electroCore, Inc. (ECOR) Earnings Call Transcript & Summary

So I'm going to go ahead and get started. Thank you, everybody, for joining us in the run up to the holiday season here. My name is Dan Goldberger. I'm the CEO of electroCore and I'm joined by my distinguished colleague, Dr. Peter Staats. We're here to talk about the core technology around electroCore that's being commercialized by electroCore and a little bit about how we see the future evolution of the company. We're so very, very fortunate to have Dr. Peter Staats. He's had a very distinguished academic career trained in anesthesiology, founder -- cofounder of this company almost 20 years ago. Continues as our Chief Medical Officer, is in parallel to all of the important activities he have a on the academic side as well. This is being recorded. [Operator Instructions] And this presentation is being recorded and the materials will be available on our website probably after the holiday. Because we're a public company, we have the usual disclaimers about forward-looking statements. And with that, I'm going to turn it over to Peter. We're going to talk about the vagus nerve, the history and science of vagus nerve stimulation and clinical progress. And then Peter is going to turn it over to me to talk about the product pipeline and commercialization. So the vagus nerve, Dr. Staats.

Well, thanks very much, Dan. It's a pleasure to be here, and it's a pleasure to still be working on this after so many years at this important area. I sometimes think of the vagus nerve as the next frontier in medicine because of the profound impact it has on bodily functions and the fact that it's been completely or partially undiscovered into the last 15 or 20 years where we've been working on it, I think, in part. Just to level set everybody in the audience, I know people come at this with a slightly different background. And I wanted to just take a moment and say what the vagus nerve is and where it fits into your body. Your body has 2 sets of nervous systems, effectively, what's called your autonomic nervous system and what's called the somatic nervous system. Now everybody is familiar with what the somatic nervous system does. That allows you to touch and feel your world, allows you to walk. It allows the motor nerves to fire. And that aspect, I think, is what we typically think about. The other aspect is the autonomic nervous system, and that's broken up into 2 separate parts. The first part is, in fact, the sympathetic nerves or the fighter flight nerves, and the second part that is incredibly important is the parasympathetic system. And the main branch of the parasympathetic nervous system is the vagus nerve. Now when I was an anesthesia resident also many years ago, what I really knew about the vagus nerve was don't touch it when I'm placing a central line. But it turns out the vagus nerve is incredibly important. It provides all of the information from your visceral structures. You see here the liver, the kidney, the small intestines, the lungs, the heart, you see these various structures. They give the information up to the brain about what's the state of the art of the body. Tells you that you're hungry, may tell you that you've got inflammation going on in your body. And in return, the brain gives information back to the structures, it's the command and control, so to speak, about how to function. Now on the left side here, you see various different functions, and I'm going to highlight a couple for you here today. First, the brain function. I mean the brain function is incredibly important. It is the counterbalance to the sympathetic nervous system or that fighter flight. It's what I call the rest and relaxation and recovery sets of nerves that your body is craving all the time. I became interested in this very early on because of the importance in bronchodilation. My son had peanut allergies, and we were looking for a way to bronchodilate it when the lungs go -- start to collapse. Other areas that you'll be hearing about in the future is gluconeogenesis with these GLP-1 inhibitors that you've been hearing about. You're going to be hearing more about that down the road. Gastrointestinal import is clear. And then I would also draw your attention to the last bullet point, which has been underappreciated until 20 years ago, is that your body can control inflammation via the nervous system. It's kind of in a strange concept of many, but it is the command and control of inflammation in the body. It controls a systemic inflammation. So this vagus nerve does an awful lot and a lot of good throughout the body. Next slide, please. Now people have been studying the vagus nerve for quite some time. Really, since the 1880s, people started to have very crude approaches to stimulating the vagus nerve in people with epilepsy. This was developed further in the 1940s in an animal model of giving toxins to the dog in particular. They were able to block seizures from happening with vagus nerve stimulation. I fast forward to the 1980s where they started doing human studies with implanted devices and in 1997, the first approval or clearance for FDA implanted device for epilepsy was obtained by Cyberonics, which is now LivaNova. 2002, it was noted that in some of these patients with severe epilepsy, their headaches went away. So that was -- it's about a 20-year history that we've known that this can control migraines. 2004, Tom Errico, JP Errico, Charles Theofilos, myself and a few others started to work on this in the more targeted way. 2005 brought us the implanted clearance for depression. What you're going to see is going to be relevant in what we're going to be talking about today. 2017 brought electroCore its first FDA clearance for acute treatment of episodic cluster. And subsequently, we have 6 different clearances in primary headache disorders, including migraine, cluster, paroxysmal hemicrania, hemicrania continua, adolescent migraine all today. Yes. Now this is kind of an interesting topic here. So I'm going to spend a few minutes talking about the mechanism of action. And I know that we're not all scientists out here. But this mechanism of action is something that leads us, that drives us, directs us towards our new therapeutic targets. I've outlined for you a couple of the things that the vagus nerve controls and vagus nerve stimulation does. Number one on my list is neuroprotection and modulation of inflammation. It does it in the periphery, as I said earlier, with the control of the spleen, but it also does it in the brain with the microglial cells in the brain, it can control inflammation. It can mitigate pain responses, and we've shown that in both animal and human models. It affects cortical spreading depression, that's waves of hyperactivity or electrical hypersensitivity of the brain. It can dampen it back down to a normal state. It affects neurotransmitter balance. So we tend to think about drugs in many of the different diseases we treat. That occurs typically through neurotransmitter modulation and the vagus nerve controls neurotransmitters, notably serotonin, which you've heard about before, noradrenaline or epinephrine and glutamate are some of the ones that we hear about all of the time. And as we start to talk about disease states today that we're going to cover, that controls the autonomic nervous system, blood flow, and that's going to turn out to be relevant to disorder, such as PTSD, opioid use disorder. Now another way of looking at this problem is that the parasympathetic is simply the counterbalance to the sympathetic nervous system. A quick search will note that many of our psychological colleagues are starting to really tune in to the impact of the vagus nerve on controlling both health wellness and disease. My good friend, Steve Porges came up with the Polyvagal theory. And this basically suggests that the body can't heal itself if it's in a state of constant threat and we need to optimize our parasympathetic tone by activating what's called the dorsal vagus. And so this is an area where I do see many different areas of medicine and study are somewhat coming together and a lighting on the vagus nerve. Next slide. Okay. So here is a diagram of the mechanism of action as it relates to post-traumatic stress disorder. I'm going to start over here on my right side and say, yes, we know about inflammation. We've talked about inflammation and how important that is to me in studying different disorders. Doug Bremner has done some really seminal work in studying posttraumatic stress disorder in humans and showing that in a stressful environment, you can mitigate the inflammatory response that occurs yes with posttraumatic stress disorder. So I -- he showed that IL-6 is dampened. And normally, there's a spike in patients with PTSD, who are exposed to stressful environments like a traumatic script. And we're able to mitigate that bump that we see in inflammation. We also know about changes in other neurotransmitters, such as serotonin, acetylcholine and norepinephrine. All of these ironically help with relaxation. We think about norepinephrine as an excitatory, but in the brain, it functions to relax the individual. It modulates circuits and fear. So specifically, there are fear circuits that occur in the amygdala, insula and other areas of the brain that this shows -- has been shown with pet imaging studies to modulate those responses. And of course, we'll alter neuroplasticity, which was originally shown in our -- some of our original headache work. So the mechanism of action leads to improvement in outcome. And in his first study, Doug Bremner, showed improvement in what's called the PTSD checklist scores. So how anxious how debilitated people are, are significantly improved in -- as a result, I believe, of these various mechanisms of action. Next slide. So we also have -- we somewhat built on our original work in headaches where we were looking at trigeminal allodynia in an animal model and we showed that we could modulate glutamate, the most prominent excitatory neurotransmitter in the brain gets upregulated in diseases such as migraines. And we were able to show a really kind of a reversal back to normal that correlates with improvement in trigeminal allodynia. We also were shown in humans that we could modulate the pain response in the trigeminal distribution. And these effects last for an extended period of time. I have here up to 3 hours after stimulation. It's actually longer than that. In some of the animal models, it's 6 or 8 hours. And it's partly just -- we don't know because we haven't studied them out far enough, but people can report a reversal of the sensitization and blocking of headaches in fact. And we've also found that you can stimulate the vagus nerve on one side and get bilateral relief. And that's partly the way that the nervous system works with the branches going up to the nucleus tractus solitarius and branching out from there, it crosses bilaterally. So we don't need to stimulate on both sides to get a bilateral effect. And this can be done with as little as 2-minute stimulations with the gammaCore device for cluster and migraine as well. Next slide. Now cortical spreading depression is kind of a new concept to some people. And I think it's important to stop and think about what that is. These are ways of abnormal electrical activity that course across the brain. And we think about our patients with epilepsy, right? Or epileptic patients, you may note that they start to have waves of activity starting in their right hand, then it goes up their arm and courses across the brain and your body basically sees this in these abnormal electrical signals. We also see that with migraines. Migraines, you may feel sensation in your arm or a visual hallucination or have an aura of a certain type of smell that occurs. And over time, you get these electrical activity changes that course across the brain. Now what Dr. [ Ayada ] did up at Harvard was he stimulated an animal who he listed a cortical spreading depression, he did it in different ways, but was able to block that cortical spreading depression, this abnormal electrical activity. And this appears to be related to both inflammation as well as some of these neurotransmitters that we've been talking about, norepinephrine and serotonin. And it's likely due to a central effect at the nucleus tractus solitarius. Next slide. Now one of the areas that I think have been really important is the realization that vagus nerve stimulation blocks nerve inflammation. And this is somewhat built on some of the work that Kevin Tracey did more than 20 years ago. And he identified what's called the cholinergic anti-inflammatory pathway. And he identified this in the periphery, really at the spleen, where the vagus nerve, if you stimulate the vagus nerve, it activates the celiac ganglion, which releases norepinephrine on T cells. T cells then release acetylcholine, which can modulate the production of pro-inflammatory cytokines. I know that's a mouthful. If I want to just break it down for you, vagus nerve stimulation blocks via a couple of pathways the production of these pro-inflammatory cytokines, TNF alpha, IL-6, IL-1 beta, HMGB. These are associated with inflammation, and we can block that with vagus nerve stimulation. And there's a number of studies going on with implanted devices now for rheumatoid arthritis and other types of problems as well. With this recognition that this does some of the same things that TNF blockers can do, we can do with vagus nerve stimulation. We upregulate norapronephrin, acetylcholine, which is really important in things like memory, laying down new memory and serotonin, which is important in sleep, as you know. And because of these mechanisms of action, we're looking at a variety of different areas of interest. Ischemic and hemorrhagic brain injury, traumatic brain injury. We're looking at long COVID and the impact of some of the theories around long COVID is that there's persistent inflammation, which, of course, we've talked about why that would be helpful. But it's also thought that one of the other main theories is that there's damage to the vagus nerve. So there's lots of reasons to think that this might be part of the solution for us. Next slide. So in summary here, what I hope to -- in a very short period of time, explain a few mechanisms of action. And these mechanisms of action drive the area of interest of clinical areas to study. Modulation of autonomic nervous system. And that's going to lead us down the road of looking at things like anxiety and stress, posttraumatic stress disorder, opioid use disorder, the autonomic nervous system here, cortical spreading depression. We've talked about headaches and other areas that abnormal electrical activity or input could come in. And we're not going to talk too much about some of those other areas. But what we did find is that we do in a headache model, it takes several weeks for topiramate or Topamax to modulate the cortical spreading depressions. We do the same thing that we can do, get to it eventually with drugs in 30 minutes where it takes several weeks to do that with topiramate. Modulation of inflammation. We talked about the pro-inflammatory cytokines. We actually showed it in acute study with acute COVID, modulation of C-reactive protein and some other changes in IL-6 in particular. And then finally, modulation of pain has been noted with vagus nerve stimulation as well. Next slide. So this is -- we are a small company, but we are punching above our weight, I would say, so to speak. I'll defer to Dan on that. But we're looking at a lot of different things right now. And fortunately, we're not paying for most of them. We're looking at post-traumatic stress disorder, as mentioned. Studies are going down at both the Emory VA as well as the San Diego VA and looking at different physiological states, looking at memory, looking at stress response, quality of life metrics in our veterans with PTSD. Another area of interest is opioid use disorder. Opioid use disorder is one of the big problems we're facing in America. I had the fortune of serving on the health and human services task force looking at best practices around opioids. And opioid withdrawal is a major problem. When we stop patients from opioids or patients with true opioid use disorder, and mechanistically, I've explained to you some of the autonomic dysfunction that can occur. And it makes sense that this will work as well. And there's some preliminary work that's been published on that as well. Alcohol use disorders, work going on at the San Diego VA and then in animal models, looking at how TBI can relate to post-traumatic stress disorder and addiction and how VNS may potentially modulate this. And so there's a lot of work going on across the neuropsychiatric domain. Next slide. So again, here, so I guess I'm summarizing here, there are currently 9 studies that mostly came out of Emory looking at PTSD, the PTSD checklist scores, modulation of the autonomic and neurobiologic response. It's not just that these patients are anxious, there are actually brain changes that can appear to be reversed or mitigated with vagus nerve stimulation in patients with PTSD. In a recent publication, declarative and working memory was improved, modulations of heart rate variability have been noted. And this all occurs because it modulates brain activity through the nucleus tractus solitarius to critical structures in the brain, including the cingulate, hypothalamus, insula and amygdala, all get up or modulated during a fear response that can be mitigated with VNS. So all of these are in critical, critical ways of actually treating the underlying cause of PTSD and not just treating a symptom. Next slide. Now some of the work that I just mentioned was presented to the FDA. The FDA did grant a breakthrough designation back in January of 2022. And there's ongoing discussions with the FDA around the pathway forward for a full clearance on this device. Next slide. Substance abuse disorder, I mentioned, is incredibly important. It's -- we can believe that we can modify withdrawal, shorten the detoxification period and potentially lead to an easier path forward to a Rivotril or another drug such as that. We believe, and there's data in both animal and human models that we can decrease the behavioral and physiological responsive withdrawal to opioids with VNS as well. Next slide. How about -- so I mentioned at the outset, we're not paying for much of this at the NIH through its branch called NIDA. The National Institute of Drug Abuse, has given Emory a large grant of $6 million to study this more thoroughly in humans, and those studies are ongoing right now. Now some of you might be thinking, okay, Dr. Staats talked a little bit about modulation of inflammation in the brain. What are the other areas that are associated with inflammation? Well, one is Parkinson's disease. And the first of a few studies rolled out a couple of years ago now and was rolled out in nature Parkinson's and they looked at freezing gate. Now freezing gait is a critically important problem. And the gait problems associated in Parkinson's is what can be lethal. Patients with Parkinson's ambulate. They don't turn quickly. They don't have a good balance. They don't have -- they have more of a shuffling gait. They fall, they can break their hip and that is what can be lethal for them. So the group -- and this was Mark Baker's group, but it was performed in India, looked at 33 subjects in a double-blind crossover trial, looking at patients with Parkinson's gait. And what they found was an improvement. And if I go to the next slide, Dan, on the left, the bar graphs here, you'll see the improvement in ambulation, velocity, step length and stance time. All of those are really important in Parkinsonian gait. Now what was also noted and you get one of the themes of my presentation here is that there is a decrease in the pro-inflammatory cytokine TNF alpha. And those seem to correlate with improvement in function. There was an upregulation of glutathione and you can think of glutathione is somewhat of a scavenger for some of these pro-inflammatory states and improvements in BDNF, which is like a nerve growth factor. And so that can potentially take us down the road of -- are there things that we can do long term. Now this is very, very early, but these are some very intriguing early steps. If I take you back to the last slide, Dan, I'm sorry to make you do this, but the last slide, my last bullet point is there is another study enrolling at the University of Newcastle, 40 patient subjects looking at gait mobility and some of the same metrics that we've been very interested in to replicate, see if this can replicate an improvement in Parkinsonian gait, which frankly creates a new option for people beyond the deep brain stimulator, which is probably the state-of-the-art. Next slide.

Peter, I'm going to interrupt you here. There are a couple of questions I'd like you to address. The first one, and I'm paraphrasing a little bit is can VNS harm a perfectly healthy person that doesn't have any of these medical conditions? And can we prevent or reduce inflammation in other maladies in a healthy person?

So the answer to both of those questions are no and yes. And I won't tell you what, no, I'm kidding. The first answer is we don't know. There has not been any sign anywhere that stimulation of the vagus nerve can be dangerous. And in fact, some of those early studies that I mentioned with the epileptic patients with an implanted device. Actually, they take an electrode, coil it around the vagus nerve and they stimulate 30 seconds on 5 minutes off throughout a 24-hour period. And they've not shown over the extensive period of time that, that can be dangerous on any other organ system, et cetera. So the first answer is we don't really have a sense that stimulation of the parasympathetic is bad. In the vast, vast majority of patients, who have been treated with our therapies. So we -- so the short answer is I don't think so. I think this is something that we can optimize and potentially help with. Now the second part of the question is, can you modulate inflammation in healthy people and potentially lead to some good long-term benefits? Well, I certainly hope so. And Imanuel Lerman has done a study on taking normal human healthy patients, subjecting the blood to lipopolysaccharide and some other types of inflammatory mediators. And then taking that same patient population and stimulating the vagus nerve before they subject the blood to that. And they were able to show a decrease in some of those same pro-inflammatory cytokines. So the answer to that is in a healthy person, it appears to dampen any inflammatory response that you're going to see from any minor injury or bacterial infection or viral infection or leaky gut or any of these other areas. And I believe personally that inflammation is central in a lot of different disorders. And if we control inflammation by what other means possible by using an anti-inflammatory diet, that's important. Sometimes it's not enough and things like vagus nerve stimulation potentially could be helpful in that population.

So thank you, doctor, and there's a second question if stimulating the vagus nerve can impact multiple tissues? How do you ensure that we're not impacting any off-target tissues?

Well, that's actually a really great question. And one of the top questions that I get. And the NIH is actually funding a large grant to tease apart the vagus nerve in animal models and see if we can isolate specific fibers to go into the pancreas, that goes to the liver, that goes to the colon, et cetera. My view is actually a little bit different. We've known a beneficial effect on glucagon and insulin and colon constipation and mood and anxiety, all of the benefits that we see with this, let me just reiterate, rest relaxation and recovery nerve all of the different structures that you're stimulating actually tend to benefit from this. We've not seen downside by going to an off-target area. And to me, I'm not even worried about that. If a patient comes in and getting treated for severe migraines and lo and behold, their anxiety or anxiousness or mood improves or their sleep improves, and that's not so bad. That's a positive benefit. It's unlike some of the other drugs where we really do have to be worried about developing the tuberculosis if we do something. We've not seen that here at all.

Thank you, doctor. I'm going to skip over. There's a question about intellectual property that I'll deal with later on in the talk, but skipping ahead, there's a question here. Any help with celiac and or Alzheimer's.

Those are great questions. Dan, you'll have to increase my budget to answer those questions on all time.

Moving right along.

Because I do think there are possibilities, particularly with that. And celiac maybe, that one is associated with inflammation. There's a fair amount of data out there on inflammatory bowel disease. [ Bruno Bonder ] actually did some of the original work on that with an implanted device. And I think he studied 7 patients who he implanted a vagus nerves stimulator on. And I think all 7 of them went into remission of their IBD. So the cholinergic anti-inflammatory pathway that I discussed in the spleen, I mentioned in the brain, also exists in the gut. And it can mitigate or modulate that inflammatory response in the gut. And since there is some inflammation going on with celiac, the answer is maybe. It doesn't get to the underlying cause, but the answer is maybe.

All right. I'll let you return to the NFL Players Association grant.

Sure. So post-concussion problems, it's actually got the news again, lately of the CTE that's occurring in professional athletes, high school athletes, and post-concussion problems remain a significant problem. We've had a number of conversations over the years with the NFL about this, but most recently, the American Society of Pain and Neuroscience, which I'm a member, submitted a grant to the NFL that was interested in things like cannabinoids and other novel strategies for NFL players and elite athletes, and they submitted a grant that's going to take a look at both cannabinoids, standard of care and vagus nerve stimulation in patients with post-concussion that study hasn't gotten started yet, but it's a funded study, and it will probably get started in January, February of 2024. Starting to take a look at elite athletes, men and women, who are suffering with post-concussion headaches. So they're starting to understand the impact of that chronic trauma causing inflammatory processes. Another area that's really exciting to me and is probably a talk in and of itself is what happens after a stroke there have been hundreds of drugs that have been tried for this and for the most part, failed. In the animal models, the group up at Harvard started to look at this about more than 10 or 15 years ago, and they showed that in an animal model, you could create an occlusion of the blood supply to an area of the brain that causes an injury, as you would suspect. What's less clear to the nonphysicians on the group here is that injury grows over the next 24 hours. That area is called the penumbra, the area at risk around the original area of injury. What was found in the first study, it was about 40 patients showed that if you stimulate the vagus nerve in -- first of all, in animals, if you stimulate the vagus nerve in an animal model, you can decrease the growth of that penumbra dramatically, and that's associated with modification and modulation of that inflammatory cytokine. In humans, in the first study that was done published about a year or so ago, they were able to show that vagus nerve stimulation, again, modified the growth of that penumbra really dramatically. So it's a really interesting finding. And there is a subsequent study being done in Leiden in the Netherlands and they're nearing enrollment with about 150 patients. So that's going to be an exciting avenue for somebody for patients, who are having an acute stroke to see if there's something that we can do to keep the stroke from being as damaging as we all know, stroke can be. It's really a -- it's a tremendous problem, and this is potentially a new treatment strategy. Again, you understand that this is, I'm not advocating you do this today, but this is part of the process that we're using to figure out what's the best treatment strategy out there for patients with an evolving stroke. Next slide. Okay. Switching gears. As Dan will talk about a little bit in more detail, we're interested in wellness as well. There has been information about depression anxiety in implanted devices for some time. And we're switching gears to take a look at how does this work in wellness. The first study with noninvasive cervical VNS showed, and I'm just going to highlight over on the right side, that patients had improvement in focus, energy, general mood, sleep, stress sense of well-being, such as anxiety, and they went from 1 to 10. They showed how much improved they were, and it really comes up pretty close to 7 to 8, a significant improvement in an open-label study. This is on the left side, you see what they were looking to get. But on the right side, they actually had really significant improvements in all of these different domains you see here. Next slide. Another area that's extraordinarily exciting to me and if some of you look around, you'll see that I have some wounded warrior paraphernalia here. I'm a fan and trying to help our returning soldiers, but also we're very devoted to our veterans and current soldiers. And unbeknown to some of us, the U.S. government is also very interested in vagus nerve stimulation for slightly different reasons. They've been looking at [ cAK ] enhancing responses in basically the drone operators. They've looked improvements in cognitive skills in sleep -- after sleep deprivation. And they've also showed improvement in mood with some of the sleep deprivation tools. And they did very exquisite studies. They're looking at improvements in language recall. And these are all really important things. I wish I had this when I was a medical student to improve my new language of understanding microbiology as well as improving my mood as well as helping me make good decisions after sleep deprivation. You can see the applicability of this really very robustly beyond just the military. I don't have all of the details to tell you all this. They've been working on this for some time. There is sometimes a little, as you would suspect, secretive and keep some of their cards close to their chest, but every time they roll out a new study on the importance of VNS in helping our athletes -- not our athletes, our warriors. VNS is turning out to be a very powerful tool in making our super soldiers even more super. So this is really an exciting area for us as well.

So thank you, Peter. And just to be clear on this slide, we are aware confidentially quite a bit of human performance work that Air Force special forces and Army special forces are doing very little of it is in the public domain, and so we're not able to talk about it publicly as much as we perhaps would like to. But it's very exciting work under the banner of human performance for otherwise healthy individuals, which is very different from your experience in mind going back many years in disease states.

There were 2 other questions here that I am going to not answer because they get into proprietary trade secret information. But one of the questions is the program gammaCore stimulate with different frequencies or for different time periods for headache versus PTSD. That's in the trade secret and ultimately, patent domain. So no, I'm not going to answer that. And then another question here, do you see changes in the dynamics of stimulation, amplitude or frequency changing the efficacy? Again, that wanders into proprietary information that we appreciate the question, but I'm going to respectfully duck the question. So Peter, thank you very, very much and stay on the line, because I expect there will be more questions. I'm going to -- sorry, so there's a follow-up question. Is the human performance data from the Air Force and Army is something that we can access or do we need to perform those experiments independently? There's absolutely positively no way we will repeat those experiments. They're scary. And what the Army and Navy special forces are willing to do in training, I'm not willing to do personally. So I'm not going to ask my colleagues to do that. Is it something that we can access? Probably not commercially, but within the armed services community and that seems to be expanding to NATO as well. There is awareness of the benefits to human performance, primarily cognitive performance and so they talk about it amongst themselves, but we are obligated by our confidentiality and we want to respect that as...

Yes. And just to add they are -- I'd just add, they are slowly publishing some of these papers, and we have some of those papers that they have published and what's in the public domain that we can share.

So I'm going to move on to some of the more mundane commercialization tactics and Peter will stay with us in case there are additional science questions. By way of review, this is our flagship product that we call gammaCore Sapphire. We currently have 6 FDA clearances for a variety of headache conditions. What I think the audience is more interested in is how do we commercialize the really fascinating science that Peter has just been talking about. So we talked a lot about PTSD, posttraumatic stress disorder. We are working with the FDA as we speak on a 510(k) De Novo submission to expand our label to treat the symptoms of PTSD with noninvasive vagus nerve simulation. Everything that I've ever done with the FDA, the timing is uncertain. But we've had a couple of rounds of questions and the questions are I put them in the category of looking for reasons to say yes. So I think this is not a question of if, but it's a question of when we'll be able to say more publicly what the time line is to getting an explicit label extension to treating the symptoms of posttraumatic stress disorder. Peter talked about the NIDA, NIH grant around financing a pivotal trial on the use of vagus nerve stimulation to treat the symptoms of withdrawal from opioid addiction. We think that data will read out in 2025. And then based on that data, I presume, and we've kind of preview this with the FDA somewhat that it will be a regular 510(k) pathway with the FDA. And so that's something to look for in 2025. The Parkinson's trial that Peter talked about, that is on track to complete enrollment into 2024. Again, based on those results, we will enter into discussions with FDA about a regulatory pathway and that 40% -- that 40-subject trial may be enough data, I can't tell for sure right now. Similarly, with the stroke trial that is enrolling in Leiden. We'll see some of that data in early 2025 as they complete their follow-ups and we'll have a similar conversation with the FDA. Wish I could be more specific about those time lines. But as you know, the regulatory authorities are not always forthcoming, nor do they stick to a strict calendar. So just to summarize, you should be looking for an announcement about PTSD in the first half of next year and then announcements about opioid use disorder as we roll into 2025. In parallel, we have dramatically expanded our product offerings. A vast majority of our business is prescription headache right now, with our flagship product, the gammaCore Sapphire, and gammaCore will continue to be the brand that we talk about for all of our prescription medical indications. Many of you, if not all of you are aware that we launched a direct-to-consumer general wellness product under the Truvaga brand. This is the product that we are currently selling. And in human performance, a lot of the work to date has been done with a modified version of the gammaCore Sapphire. Going forward, we've hinted in some of our public conversations about this product configuration that we're now calling Truvaga Plus. This is a streamlined direct-to-consumer general wellness device that communicates to a mobile phone app. So not only are we going to have a more competitive, more contemporary looking general wellness device, we're now explicitly entering the digital health, digital wellness community. And we think the sky is the limit for that combination of a vagus nerve stimulator and a digital health application. On the prescription side, you will see an evolution of gammaCore Sapphire into a more streamlined, more flexible format. And we're also working on wearable implementations of our prescription therapy. Not so -- that wearable formulation is not so important for personal use devices like headache, but as you get into Parkinson's, as you get into stroke where the patient is less able to self-administer the therapy, that wearable opportunity becomes more and more important. On the human performance side, Air Force research laboratories helped us design a mill spec version of the gammaCore Sapphire. This is in prototype from. Now we are working towards commercialization, and we expect that this heavy-duty mill spec version of the gammaCore Sapphire that we call Tac-Stim will supersede what we're currently selling to the Air Force and Army today.

So there were several questions around intellectual property. We have really 2 pillars in our intellectual property platform. The first is around noninvasive stimulation of the vagus nerve at the neck and the reason I emphasize noninvasive is that there is a pretty large right to practice that stems from the fact that implanted vagus nerve stimulators became available in the late 1980s and were commercialized in the 1990s. So we have a broad field around intellectual property in vagus nerve stimulation that's available to us, because it's an old technology but the new piece and the protectable piece of this technology is the noninvasive transdermal treatment method. The second pillar of our intellectual property is around digital health. We were early filing intellectual property about connecting a medical device to a mobile accessory to a mobile phone. We are tracking a surprisingly large group of potential infringers of that intellectual property portfolio for the time being. We've chosen not to be aggressive. But as the company gets stronger in the future, you may see us taking some steps to assert our digital health portfolio. We continue to file for additional patents, both as stand-alone patents and continuations to the matters that we have pending as we explore additional disease states. And as Peter and his colleagues uncover more detail around the methods of action. So how do we monetize some of this? The headache market. You've heard me talk about this quite a bit. Sorry, I'm going to jump back to some of the questions. There's a question here about is the design of the Parkinson's and stroke trials publicly available? Yes, those trials are posted to clinicalstudies.gov. And if you contact me after the talk, I can point you in the right direction or you can search for them directly. And then there's a question here about price point in our different channels. And again, I'm going to hide behind the trade secrets notion that, yes, we have different pricing strategies in our different channels. But our direct-to-consumer channel, you can go to our website, truvaga.com, and see what our current pricing is. We may or may not be doing a Black Friday offering on truvaga.com. So the headache market, the patient advocacy groups will tell you that there are tens of millions of Americans that suffer from headaches and specifically migraine. In practice, about 2.5 million Americans have a prescription therapy. And so I really see that as our total addressable market in headache. Triptans are the first line of therapy in prescription headache, followed by the injectables. And for the time being, especially in migraine, neurostimulation remains a distant third in sort of the continuum of care. That said, in cluster headache, which is about 400,000 patients in the U.S. noninvasive vagus nerve stimulation, specifically gammaCore Sapphire has been identified as a first-line therapy in cluster, because there are very few pharmaceutical options and the ones that are available are expensive and difficult to administer. One of our big channels -- for those of you who have been following the company for a long time, one of our big challenges has been the competition with Big Pharma in headache. But in the VA hospital system, which is our single largest customer, there are about 600,000 headache patients. We've treated not quite 4,000, so we're less than 1% penetrated within the VA hospital system, our primary revenue generator. So we have plenty of room to run within headache, and I'm very much looking forward to expanding our horizons beyond headache in the future. Posttraumatic stress disorder, as I mentioned, is next up for extended indications on our prescription brand, gammaCore. Roughly 8 million Americans. We often think about PTSD associated with military service, but unfortunately, there's an even larger cohort of PTSD sufferers related to domestic violence. It's a shame that that's part of our society today, 46 million Americans, I don't know, but that's in the literature, 8 million Americans currently diagnosed. Opioid use disorder 3 million diagnosed right now. Unfortunately, as everybody is aware, that's a growing category. The launch market, if and when we do get a label in opioid use disorder will be as using vagus nerve stimulation as a bridge to Rivotril therapy initially at least in residential treatment programs. So again, because we already have a channel in the VA hospital system launching PTSD in the VA hospital system makes all kinds of sense, launching opioid use disorder in the VA hospital system makes all kinds of sense. Parkinson's disease. Fortunately, it's a much lower prevalence, but we think we have a very interesting targeted therapy there. And so I'm optimistic that if the data continues to come in, in a positive way that we've got a commercialization path for Parkinson's, especially in rehab medicine in the continuum of care as well as some of the other indications that Peter was talking about. Let me pause here to take a look at some of the additional questions. Are you going to partner with any large established medical device distributors to accelerate the ramp of sales? There is nothing imminent in the way of partnering. We do believe strategically that some of these markets that are available to us, concussion, stroke might be better served by a distribution partner. Outside the United States, we have a distribution agreement with [indiscernible] Pharmaceuticals for Japan, we have distribution. We have distributors in Australia and in parts of Western Europe for our current products that we would extend to our future products as well. Moving on to our direct-to-consumer initiative. For those of you who've been following the company, we've been surprised to the upside with the efficiency and the metrics of our direct-to-consumer launch, all very small numbers right now, but the digital health and wellness market is huge and getting bigger every day. We have a very unique offering, and we have quite a bit of intellectual property in this space. with the budgeting process that we're going through with our Board right now, the launch of Truvaga Plus sometime next year. I think you're going to see this become a larger revenue and more and accelerating revenue contributor to our long-term business. So the summary that I'd like you all to take away, we're going to continue to grow our prescription noninvasive vagus nerve stimulation. The VA hospital system in the U.S. is our largest customer. The NHS, National Health Services in the United Kingdom is our second largest customer. We've talked about the distribution agreement we launched with Joerns Healthcare that gives us access to another 12.5 million covered lives beyond the 9 million VA hospital covered lives. So slowly, but surely, we are increasing the number of covered lives that have access to our therapy, and we're going to continue to work towards broader indications and broader insurance coverage for our prescription business model. The Truvaga direct-to-consumer business, please go to truvaga.com and take a look at what we're doing there. That business in the short term is going to scale with our advertising and promotional spend, look for us to launch Truvaga Plus, our first app-enabled vagus nerve simulator in the first half of 2024. We're very excited about working -- continuing to work with our champions at Air Force Research Laboratories, Air Force Special Operations Command, United States Army Special Operations Command, where we've been upside surprised by some of the pilot deployment orders and the feedback that we're getting about human performance. Longer term, and I think some of the questions we're heading this way. We think there's a large opportunity for civilian crossover in our human performance product line to first responders, to elite athletes, to transportation, health care shift workers on and on. And then those of you who are following the company know that we improved added to our balance sheet over the summer. And we really believe that we've got adequate financial resources to execute on this plan through 2024 into 2025. And growing the business and the cash flow that comes from that business. There's a question here that just came in about timing of the opportunity with Joerns Healthcare to becoming more meaningful. We did report a small amount of revenue in the third quarter. The current quarter will again be a small amount of revenue. It's going to be very similar to the first year of our work with the VA hospital system in 2020. We did -- with our first full year of sales in the VA, we did roughly $1.5 million of revenue. And so I'd like to see us meet or exceed that in 2024, which would be our first full year of working with the Joerns Healthcare system. That concludes our prepared remarks and shocking, Peter, we're more or less on time. I hope this was useful and great to get some meaty questions from the audience. Peter and I and the rest of the management team, we all try to be available to the investment community and our existing shareholders and prospective shareholders. So please don't hesitate to reach out to either one of us or through the Investor Relations e-mail that's available on our website. We'll do our best to be responsive. I wish you all a very happy and healthy holiday season coming at us very, very quickly. And I want to thank all of our customers and physicians supporters and our supporters in the armed forces. Thank you all, and have a great day.

Happy Thanksgiving, everybody.