Hello everyone, thank you for joining a Vistagen Therapeutics presentation here. I am Vishwa Shah, one of the associates here at TD Cowen with the biotech team, and it is my pleasure to introduce Shawn Singh, the CEO and Director of Vistagen Therapeutics.
Great, thanks, Vish. Appreciate the opportunity to speak in front of all you today. Thank you for spending your time with us. As always, we'll be making some forward-looking statements, so please refer to our SEC filings for any further questions. What we're here to talk about today really is a new class of medications that we've got a team internally that's been pioneering this, this new class called Pherines for a couple of decades. So our focus as a company is really to establish entirely new standards of care across multiple indications using this platform, using this technology that's associated with, really effectively using the nose as a portal to achieve, really significant behavioral and physiological changes. So our focus is on psychiatric and neurological disorders.
We've got a pipeline right now that consists of 6 clinical stage assets, and I'll show you in a minute, what those are, plus others that are in the preclinical stage. So we're looking only at markets that are significant, that are large, that are, underserved currently by the FDA-approved therapies in that space. We've had some very significant history-making data, in a disorder that hasn't seen anything for decades in a phase 3 context, and especially with an asset that doesn't have to go through your whole body or get into your brain to achieve the behavioral effects that we're seeking. We'll talk more about that, as well as the rest of what we have in place right now and funded. We've got about $126 million on the balance sheet, as reported through our last Q, as of 12/31.
And that helps us to have the ability to put in place every aspect we think's needed to initiate in 2024, such that by the end of 2025 and the early part of 2026, we could be in a position to submit a new drug application with the FDA for what could be the very first acute treatment of anxiety for adults with social anxiety disorder. So here's the pipeline.
We'll spend most of our time today, 'cause it's always the case with the speed date, we can't get through everything, but the top three assets in particular we will focus on are fasedienol for social anxiety disorder, that's in phase 3, itruvone for major depressive disorder, a new monotherapy potentially for treatment of major depressive disorder, and PH80, which is an asset again through phase 2A, for a couple of indications in the women's health arena, but particular focus today on vasomotor symptoms. Maybe you're starting to see that on TV, hadn't heard of that in a while, but, hot flashes due to menopause. And, so let's talk a little bit about pherines.
I was at a meeting yesterday at Mass General, and one of the things I heard from a distinguished KOL was these Pherines are the most exciting new class of drugs in development. And we certainly agree with that. This is a class that has completely differentiated mechanisms of action, or MOAs, from the current standard of care in each of the indications that we are focused on. They are delivered intranasally because the receptors that we need to activate, the neurons that we need to activate, are only in the nasal passages. We'll talk more about that when we get into the SAD program, but these are odorless, they're tasteless, they essentially activate neural circuitry.
That's what we're focused on with this class of drugs, that is activated in the nasal passages, mediated through one interneuron, the olfactory bulb neurons, and then broadcasting forward to different parts of the brain associated with different indications. What we've noticed, and we've studied extensively, is that none of these drugs needs to be taken up systemically to achieve the effects that we're looking at. They also don't need to act directly on neurons in the brain. So as a result of that, we see significant benefits on the safety side, in particular. There's no binding to abuse liability receptors, for example, opiate, nicotine, dopamines, steroidal hormonal receptors. So that gives us a very favorable safety profile for each of the assets in the Pherine pipeline across all studies completed to date.
So particular focus, again, especially in the psychiatric disorders, are drug candidates that have rapid onset effect, but also aren't causing sexual dysfunction, sexual side effects, weight gain, the types of things that are typically associated with the drugs that have been approved by the FDA today. So let's talk for a minute about Social Anxiety Disorder. It's a very significant problem, a serious mental health condition affecting a lot of American adults and a lot of people around the world. This is a fear, essentially, and anxiety about being judged or humiliated or embarrassed in what most people consider common everyday social and performance situations. Things like a job interview, going on a date, sitting in a classroom, fearing that you're going to get called on. What we see as the onset's typically in adolescence, 13-17, but the mean duration of the disorder is about 20 years.
So it's a significant chronic disorder. The key drivers we're seeing still, pre-pandemic, it was the same as it is now, reemerging, social media, team orientation in the workplace or in an academic setting. Again, situations where there's a profound fear and a debilitating fear that results in a lot of opportunity cost in the lives of people affected by this disorder. They don't pursue vocational advancements, social relationships, things that many of us take for granted. So what we're trying to do with someone who's affected by this disorder is bring them from a very high level of anxiety in their daily lives, when their stressors are upon them, to really, I would say, a normal level of anxiety. We all need some anxiety to be energized or focused, but we don't want to sedate them, like with a benzo, right?
So there's a key to be able to maintain the ability to function at a normal level, but not be cognitively impaired, not fear that you're going to risk, abuse liability and the like. Right now, what we're seeing with reengagement post-COVID is what we started to see we saw a lot in the decades before COVID, which is an increase in the population of folks affected by this disorder. And that's, again, safe harbor in COVID because there was a good reason to self-isolate for many people. What we're starting to see, though, fortunately, the silver lining of that is the destigmatization of mental illness generally, and people willing to talk about not being okay, willing to seek diagnosis. The problem is there's not much for them to lean into.
There's only three drugs approved for this disorder, and there hasn't been anything approved for about 20 years, a little more than 20 years. They're all old-school antidepressants, Paxil, Zoloft, and Effexor. And we all know the side effect and safety profiles of those drugs, but most importantly, they're not capable of helping in the moment. So what we need is something what patients and doctors need is something that will allow a person affected by this disorder to deal with their stressor right before their stressor, which is very predictable, typically. And even if there are multiple different stressors within a particular day, to be able to use a drug candidate multiple times during that day to address each of those stressors, or a day like this where you have a conference environment, maybe the same type of stressor throughout the course of the day.
So that patient control is important, and the ability to use a drug more than one time a day if you have more stressors in that day is also important. So let's talk about fasedienol. This is our lead asset. We've de-risked this program considerably with recently announced phase 3 data last August and a positive phase 3 study and a public speaking challenge. We'll talk more about that in a minute. Again, this mechanism of action compared to everything approved, and even those drugs used off-label, is completely different. Not only the way it works to generate the efficacy we've seen in phase 3, but also the safety profile that's so differentiated from what's out there today. We know, for example, that it doesn't potentiate GABA, which is what underlies the effect of a benzodiazepine, right? The benzo epidemic out there is definitely worrisome.
And so we want to be able to provide an alternative where you're not going to impair cognition. Again, and unlike a benzo, which it's once a day, we see the ability to use a drug like fasedienol multiple times a day, up to 6 times a day ultimately is where we think we'll get to. And again, the patient's control is key, just like, say, a rescue inhaler for asthma, right? We want the patient to be able to know when they need it and not use it when they're asymptomatic, which is often the case with a social anxiety patient. When they're not exposed to their stressors, they're asymptomatic. Okay? So again, being able to, in the moment, as needed, acute treatment, is what we're aiming for. We also know we've radiolabeled the drug. We know it doesn't act on directly on neurons in the brain.
We saw a little bit of nasal drip, but again, not no detectable levels in the brain. So how does it work? Well, we have in our nasal passages neurons called chemosensory neurons and receptors to those neurons when they're activated with a small microgram dose, 3.2 micrograms. What we see then is that they will then trigger receptors in the olfactory bulb, right at the base of the brain, right above the nose. Those then will project forward to different parts of the brain, activating neural circuitry, especially directed towards the limbic amygdala, the main fear and anxiety center of the brain. And what you see there is once that's stimulated, there's a decrease in the activity of the sympathetic nervous system, and that's again what facilitates it. It's like a brake pedal for fear and anxiety.
And so we're doing that, again, activating neural circuitry in the nose, projecting to the olfactory bulb, the base of the brain, that interneuron, then broadcasting forward, in this case with this asset, to the limbic amygdala. So within about a 3-inch range, you're going using the nose as a portal to get to the parts of the brain we think cause people with this disorder to have the opportunity cost in their life that they experience for many cases, for decades. So the phase 3 study that we announced, the PALISADE-2 study, was a public speaking challenge, essentially 4 weeks. Over the course of the 4 weeks, there's 2 speeches given. So first visit is just screening. The second visit, subjects come in and they're establishing their baseline with a placebo.
They're told 15 minutes after they're given the drug that they have 3 minutes to prepare for a 5-minute speech to a group of strangers. During that speech, the endpoint that is associated with an acute treatment asset is called the Subjective Units of Distress Scale, the SUDS. So each minute during that 5-minute speech, the patient is telling the rater. So it's the patient-reported outcome. One of the key things about this program is the patient's telling the raters how they feel. The patient tells the rater how they feel on this scale, which is 0 to 100. 75, for example, means more than a little uncomfortable during that minute.
And so if they are more than a little uncomfortable in this study for 1 minute at least of the 5 minutes, they're invited back a week later and the challenge is repeated, but they're double-blind, randomized to drug or placebo. And again, 15 minutes after they get either drug or placebo, double-blinded, they are given 3 minutes to prepare for a second speech. And ultimately, at the end of the day, what they're doing is we're assessing how they did in speech 2 versus speech 1, group to group, treatment versus placebo. So what we saw in PALISADE 2 was every one of the endpoints that we cared about were hit positively. The primary endpoint was assessing how the treated group did versus their baseline against how the placebo group did versus their baseline.
So, as you see, it was stat sig, and obviously we think clinically relevant, has expanded on by the secondary and exploratory endpoints. This is the primary endpoint where we looked at about a 5.8-point change between the treated group and the placebo group. Important now to understand the clinical relevance. So the secondary endpoint was the physicians saying how they thought those in each of the groups did between speech one and speech two. So this is the CGI-I; the clinicians are rating this. As you see, more than almost two times greater the number of folks on drug were very much less anxious or much less anxious compared to the placebo group. This next endpoint is extremely important to us. This is how the patients felt they did speech one versus speech two, or speech two versus speech one.
So you see here, more than two times, the number of subjects on drug said they were much very much less anxious or much less anxious compared to the treat the placebo group. This tells us how the drug will how people will possibly be improved in their lives by use of the drug. So we really like this endpoint. This will be elevated to a secondary endpoint in PALISADE three and four. And this last endpoint is assessing the, about 2x, the number of subjects that had a greater than a 20-point improvement treatment versus placebo on the SUDS from speech one to speech two. So at the end of the day, obviously, from an efficacy perspective, that's exactly what we were hoping to see, and it was consistent with what we'd seen in phase two.
We didn't see the same thing in PALISADE-1, which was conducted primarily during the pandemic, which the black swan of the pandemic definitely had some impacts on variability and on the ability to execute the protocol. What we saw in PALISADE-2 was that the vast majority of the subjects randomized in that study were in 2022, when masks started to come down and other ability to execute the protocol with rigorous adherence was more possible than during the pandemic. So the safety of the drug in this, in PALISADE-2, was exquisite, again, no TEA more prevalent than 2%. More importantly, here in the open-label study, nearly over 30,000 doses administered over many months to up to about almost 500 subjects, 481 subjects.
And what we saw in this study, looking at them over time, was that the most prevalent treatment emergent adverse effect was headache at 8.7%. No other treatment emergent adverse event more prevalent than 5%. So for a neuropsychiatric drug, it's phenomenal. It makes sense, however, when you think about the mechanism, drug's not detectable in the plasma, it's not taken up systemically, it's not dropping into the brain and dealing and landing on abuse liability receptors, that you would typically see create the kind of safety profiles associated with current meds. So we're confident, that we can continue to see this kind of a tolerability and safety profile. The cells that we deal with in the nose turn over in about three weeks. So tachyphylaxis, tolerance, those types of issues that are associated with systemic drugs, we typically don't see, that kind of potential.
We also, at this point, when we went back to the FDA, we asked in 2022, do you think we need to do a human abuse liability study? And we announced back then the answer was no. The reason, again, because what we're seeing with what we've done in preclinical studies and in clinical studies have given us a lot of confidence that this is a significantly differentiated safety profile from what's out there. Okay, so what's left? What's next? We raised the capital last year, and the runway that we've got is intended to fund all remaining aspects of a potential NDA-enabling program for Fasedienol social anxiety disorder, the acute treatment of social anxiety disorder. That means PALISADE-3, with some enhancements, especially associated with surveillance and execution of the study, as well as PALISADE-4 to replicate the results of PALISADE-2. That's the goal.
Each of these studies will have an open-label extension to, again, bring additional subjects into the safety database and give us the ability for long-term chronic dosing. What we've seen in some studies in the past in real-world settings is the more that people use the drug, and this is again using a scale, the Liebowitz Social Anxiety Scale, which was used for the three approved drugs, looking at people over time, the more they have success in an acute setting, the greater their confidence becomes, their resilience becomes, their ability and willingness to engage in stressors that they've typically avoided. So we like this drug, obviously, in an acute setting like a rescue inhaler, but we also see its benefit over time as this disorder unfolds in people's lives that they get more confident and eventually they don't have to use our drug. Right?
They're not or anyone's truck. They're able to deal with these opportunities in their life, in the way they see is the ideal version of themselves. So the plan is to initiate all necessary potential NDA-enabling studies in 2024 and have them all read out in 2025, with the goal of early 2026, if we're successful with PALISADE three or four or both, to submit a new drug application in the first part of 2026. Okay, just a minute or two left, we'll focus on Itruvone. This is our asset for major depressive disorder. And again, what we see here is a very different, unique mechanism of action, potential for rapid onset and again, non-systemic, non-addictive, non-sedative, the type of a drug candidate that we think people are seeking to treat this disorder.
The millions of people affected with MDD or major depressive disorder want drugs that they will know, unlike current medications, whether or not it will benefit them and not wait 6 to 8 to 10 weeks to figure that out and all along the way have to endure the side effects that are very predictable associated with the current antidepressants. Our focus here is not on naive patients. Our focus here is on people that have failed probably 1 or 2 old-school antidepressants. So they're moderate to severe patients and we want to be able to give them a benefit that they can take a couple times a day to deal with their depressive disorder, but in a way that doesn't cause the worries that we think are associated with existing medications.
The phase 2 study that we did, this was a small phase 2 study, a 2A study in 30 subjects. There were three arms to the study. What we saw in the 6.4 microgram level, that was dosed twice a day, we saw a significant separation between placebo and drug. I'll show you this here. So this is the model that we'll be carrying forward into a phase 2B study, our plan for this, probably at the beginning of 2025, only because seasonality means you don't typically start depression studies in November, December, early January type frame, not because of the patients, more because the sites aren't usually around. So we're aiming for a phase 2B study, again, as a monotherapy, rapid onset effect. We'll be using the 6.4 microgram dose. We're using the HAM-D17 as the endpoint.
What we'll probably assess here is about a 6-week study designed with interim looks at about a week, 2 weeks, and then a month, and then at the end of the 6 weeks, again trying to detect, of course, the change on that Hamilton scale against baseline. PH80 is our asset, also with some significant phase 2A data in two women's health indications. I think I'm only going to have time to deal with one. What we see here is the opportunity for a totally hormone-free approach to treating vasomotor symptoms or hot flashes that are associated with menopause. And and under there's a new drugs that are out there. There's one at least that was recently approved, starting to see it on TV.
That's an oral drug, which again, when you have oral drugs, you got to march through the liver and the kidney and other parts of the body. We have a non-systemic opportunity here for, again, as needed use by women affected, the 80% of women between 45 and 65 who are, we think, seeking a hormone-free solution, but also one that might not have liver liabilities or other liabilities associated with systemic uptake. What we saw in a phase 2A study, what we were trying to achieve here was similar to the recently approved drug. We were focusing on moderate to severe. And we were trying to assess whether or not there was a reduction in the number of hot flashes as well as a decrease in the severity of those hot flashes, the bother factor, the sweating.
What we're able to show in this phase 2A study was both the number and the severity of the hot flashes were diminished through the course of this study. At through four weeks of treatment, a significant, highly statistical result. This shows the reduction in the number of hot flashes experienced by the women during the the four-week period. And this shows the severity that was associated with the reduction in the bother factor, the sweating, the irritability that's related to, to those hot flashes experiences. Again, it's important to be able to go forward with a drug candidate that we think has a very remarkable safety profile. At the same time, the ability for patients to control how and when they need a medication for something that is amenable to acute treatment, to as-needed use.
We also saw some positive data in a PMDD or premenstrual dysphoric disorder. And again, that's a severe condition that women experience upfront of PMS, and there just isn't a real good solution out there for that. So phase 2A data in that indication as well. So what it shows is this is a platform. This is a mechanistic approach to being able to use different regions of the brain to control outcomes. We have two other assets. We'll have much time today to give you, but one is for cognition improvement, especially for people affected by fatigue. So shift worker syndrome, sleep apnea that affects their ability, the reaction time. We should hear more about that later this year. Another one that's associated with enhancing appetite in patients affected by wasting syndrome, cachexia, for example.
So there's a part of the brain, the same part that's associated with body temperature that's associated with appetite. So to be able to measure caloric increase, protein level increases in people that are used often late-stage cancer patients is what we see. So again, what that shows is multiple and diverse, really large market opportunities up and down a platform that has a same lock and key approach for the first two steps of the mechanism, the chemosensory neurons to the olfactory bulb neurons. And then from there, directing it to different regions of the brain associated with what we're trying to achieve behaviorally or physiologically. So more to come as you'd expect. We have a really distinguished panel of advisors. In fact, Dr. Maurizio Fava right down the street here at MGH, for depression. Michael Liebowitz is the Babe Ruth of social anxiety disorder.
He's the principal investigator for the social anxiety program, the phase 3 program. Sanjay Mathew, Jerrold Rosenbaum, experts in depression, Mark Wallace in some of the neurological disorders, and then, Thomas Laughren, former FDA commissioner of the Division of Psychiatric Products, was very important for us. So again, it's a very exciting time for us. We're a well-funded company. We've got a broad pipeline that is full of differentiated assets in areas where we have not seen benefits for patients in a very, very long time. So it's time for a change. It's time for new standards of care. We're happy to be at the forefront of that pioneering work. So thank you for your time.