Feelings of anxiety and depression can be absolutely debilitating. And the side effects of the medication that’s supposed to make you feel better. Can I Ronica often make things worse? It’s amazing that in 2020, we haven’t really figured out a consistent, reliable and side effect, free method of dealing with these issues. My guest today is the CEO of a company that is tackling these incredibly important issues. And they’re doing it pretty successfully. Therapeutics is a publicly traded company on the NASDAQ stock exchange and has shown remarkable promise with their line of products. These products have so far been shown to drastically reduce feelings of depression and anxiety with little to no side effects. It’s really some amazing stuff. As someone who has personally suffered from anxiety, this was an incredibly exciting interview. And if you’re one of the millions of people suffering from anxiety or depression, your going to want to listen.
So without further ado, CEO of Vistagen therapeutics, Shawn Singh, the human experience is changing and it’s going to happen a lot faster than you think the world is going to be a vastly different place in the next 10 to 20 years because of what’s happening in the biotech industry right now. Welcome to the simple biotech podcast. My name is James rule, and I’m your host. The goal of the simple biotech podcast is to interview the researchers, founders, and investors that are working directly in the industry and to translate what they’re working on into simple and easy to understand language. If that sounds like something you’re interested in, let’s get started.
Shawn, thank you so much for joining me today. Hey James, my pleasure. Thanks for the opportunity to talk to you, Shawn. You’ve been with Vistagen for a very long time, for more than 20 years first joining the board of directors back in 2000 and actually becoming CEO 11 years ago, back in 2009. That’s a pretty long time to be involved with one company. So I imagine you miss really enjoy working there before we dive too much into that. I want to get to know you just a little bit better. What were you doing before this? Shawn, what initially caused you to get involved in the biotech industry? Where did Shawn Singh career ambitions first start to take form? This is a very complicated business. There’s an ecosystem that really has to be deployed to be effective, to develop a drug that’s actually going to get, especially one that gets into a human brain and does some heavy lifting benefits people. But I think it started about 30 years ago.
Almost 30 years ago. Now I was part of one big part of that ecosystem, which is the legal side. I started as a corporate finance lawyer at a big firm here in Silicon Valley called Morrison and Forester. And my job at that time as a young attorney in my twenties was to be the one who wrote the perspectives, the business section. So I kind of split my time between what were high tech, booming, IPOs and biotech IPOs at the time. And you really developed an affinity for the biotech aside. You have to ask a lot of questions when you don’t really know much, and you’re never the smartest guy in the room, or, you know, you’re in the wrong room when you’re writing these things. I learned a lot about the business of biotech and it just became clear in two fronts. One, I saw that in a very predictable future.
My wife and I did my wife now 32 years early on in our marriage. We, it was pretty clear as a corporate lawyer, not a lot of time to see kids, lots of divorces just wasn’t really the life cycle I’d envisioned. So I made a decision to really decide between the two different sectors at that time, high tech biotech, and it was clear choice to biotech. So I went in house at a company that I had just built as a lawyer about a million dollars. And I basically said, look, I can save you quite a bit of money by bringing me in house. And I made the move into a company called cycling pharmaceuticals. That time there was a focus on hepatitis and immunotherapy, and it just became fascinated by the entire process and the ability to actually make money and help people, which was, has been the driving mantra really from day one and wanting to be able to say that to my kids.
They didn’t have any at the time four kids later all now grown. I think it was probably the best move in my life. I was there through about 1999, 2000. At that time, it really, he hit me. I had a kind of a midlife crisis. This is at 36 and I got necrotizing fasciitis, the flesh eating bacteria while I was trying to scrape and tape for capital in New York. That was, that was really a close call hours away from dying. And a fabulous Navy seal surgeon came in and said, you got two choices. Either we operate in 30 minutes or you’re done. He operated. And then it was just amazing medical treatment for the next several weeks. Totally changed my perspective. I left the company that we had rebuilt cyclone and recapitalized and decided to go to another part of the ecosystem, which was the venture capital arena.
And then connected with that. What’s called the contract service contract research organization sector. He’s helped companies get through the hoops and hurdles of drug development and worked for both of those entities for about eight years. And during the course of running the venture fund, it became clear that this gin as a portfolio company was somewhere that I really wanted to focus timeline disproportionate to other companies in the portfolio. My thought at that time was there were a lot of drugs. I don’t know if you remember Vioxx and Avandia, there were drugs that made it all the way to the market. And all of a sudden people started dying because of liver toxicity or heart toxicity. Well, this Jen had and still has the technology to be able in essentially in a test tube using human cells, derived from STEM cells, to tell whether a drug is going to be toxic to the human way before even animal studies.
And that fascinated me, that technology we’ve since licensed it to Bayer or cardiac STEM cell applications. And then along the way it became clear, we could use that technology to also rescue drugs. Well, the same time I brought in a drug from the venture portfolio into Vista gin, and that was a CNS drug it’s called [inaudible]. And that developed what is currently our focus and that’s all exclusively on central nervous system, drug candidates and drugs that really are fundamentally different, not just a me too scenario, but drugs that act differently that work differently in the central nervous system, especially in the brain have a fundamentally different safety profile. I’m sure we’ll talk about benzos today. Fundamentally different side effects and safety concerns eliminating those. So an ability to move in multiple different markets or indications as we call them a long road. And, but always surrounded by incredibly talented and smart people still are. I’m still doing that. And that’s been really the biggest blessing of this career is to be able to work with just fabulously expertize people all around me and all the different disciplines needed to bring a program to near successful level where we are now with our lead truck.
I got to say, that’s a hell of a story, a corporate lawyer to a biotech CEO and sprinkle a little bit of flesh eating bacteria in there to inspire the change. I think that’s a bit of a unique story.
Aspect, you know, and there’s always a personal component. You have to have passions and real life experiences drive those passions and family members of mine. Also I’ve wrestled with mental health, especially depression. And, you know, it just became really clear that things had to change. We really had to, and I started even before COVID and I think one of the silver linings covert is starting to see this a lot more. I’ve always been the belief that we’ve just got to destigmatize mental health. You know, it used to be not that long ago when someone would get breast cancer or prostate cancer would be all hush, hush, and no one really wanted to tell anybody and saying, and now you hear that. And it’s like, okay, fine, sorry to hear it. But here’s the battle plan. Know it looks, go do this, this, this, and this.
And really the same thing has to happen with mental illness, with anxiety, with depression. It’s like, okay, this is something that we have to wrestle with. It’s real. A lot of people have it and let’s address it. Let’s bring the resources to bear some of that’s medication. A lot of that’s talk therapy. That’s actually been happening more and more as a result of COVID. That can be pretty clear that it’s not surprising that we have a mental health pandemic on the other side of this COVID health pandemics. So far a little bit of progress made there. And I’m happy to hear that it’s now the point in time where what we’ve got is even more relevant than ever before. We didn’t just sneak up on these things takes a long time. As you said, to develop a drug and long before the world’s anxiety, depression, and suicidality issues that we are all wrestling with today, we started these drugs on tracks that I think now are points to be ultimately hopefully very helpful to people.
Speaker 3 (09:26):
Yeah. I, 100% agree with you on that in general, as a society, we definitely need to not stigmatize mental health. And I think that we are making progress on that. I mean, you, you’re seeing kind of tele mental health, especially nowadays growing even more sites like better health and Talkspace that allow you to do online conversations, online therapy. So I think in general, people are coming out more and more and talking about it, which is definitely a step in the right direction.
And when you compare it to 10 years ago, yeah, no question. And we, even before COVID, when we had seen sharp increases in pressures from social media pressures, from rising team orientation in the workplace scenarios where there was just a lot more risk factors associated with anxiety disorders in particular, it just says become increasingly clear that now that has all been amplified by the verse impacts from the code pandemic, social unrest, these are real life issues that people wrestle with daily and they’ve appended a lot of lives. So it’s no surprise when it’s reported in the mass media that we have these issues universally, and that we have a system that needs to improve quite a bit. There are some advances, as you said with telehealth, and that allows a little bit more privacy. You don’t have to tell your employer that you’re going to go to a clinic and get your medication. But I think there’s a lot of room for growth.
Absolutely agree. So there are a few reasons why I’m really excited to talk to you. One of them being the, I personally suffer from social and generalized anxiety and to be able to talk to the CEO of a company that’s at the forefront of basically replacing benzos is super exciting for me. Secondly, you are the only company I’ve talked to so far. This will be actually be the 10th episode that has a few let’s call them assets that are through phase two trials. And I’m super interested to hear what that hope
That’s a whole podcast in itself. It’s clearly the case that every season is not a harvest in biopharma. There are definitely seasons where got a water plant and we fertilize and all of that’s important because you drive towards seasons where you get near the end of the line. And I think that’s where we are with pH 94 B the first of the three assets. So we have three pH 94, B is for anxiety disorders. That’s a neuroactive nasal spray with a completely unique pharmacology or the way that the drug works in the human body. And the second one is pH 10 that’s for depression related disorders. Also a neuroactive nasal spray. And the third is 81 Oh one, which is an oral pill. That is for both what we call neuropsychiatric indications, depression, suicidal ideation, and neurological. So pain and movement disorders and potentially epilepsy and other indications.
So two of those three have already been in human patients through what we call phase two studies and have generated very successful outcomes based on the statistics. So you look at the statistical probability that the result was due more to the drug than to any random chance and pinpoint Oh five is a really statistically significant value or the lead drug. [inaudible] that P value if you will, is 0.002. So highly statistically significant. And the study that was done in phase two, that is now leading us into phase three in the world of drug development, you really have an a four stages. The first is what we call preclinical development that’s before a drug gets into a human, and then there are three phases of development in human, healthy volunteers and patients. So phase one is safety based. That’s where healthy volunteers, people who don’t have the problem you’re trying to address are assessed for the safety of the drug.
Then you move into phase two. If the phase one safety data are sufficient, then you have phase two development in patients. And in patients. Now you’re trying to test both safety and efficacy. Does the drug work with pH 94, B and pH 10, both have had successful phase two studies and pH 94. B is the most advanced now moving into phase three, which replicates phase two on a larger basis, somewhat larger basis in many cases. And you do two of those studies, they’re called adequate and well controlled studies. Those then support the total body of work that is under what’s called a new drug application that you submit to the regulatory authorities. In our case here in the U S the FDA for approval to market the drug. So we’re at that last stage with pH 94 B for anxiety disorders in particular social anxiety disorder, entering phase three, a early part of next year, and hopefully of successful.
Then we will have for the first time a drug that can treat acutely on demand as needed the anxiety that adults with social anxiety disorder experience. And as I understand, you’ve experienced, so what’s needed is what we don’t have anywhere in the world. And that’s exactly we’re headed for is to try to become the first ever FDA approved on demand as needed treatment for that case where you can often predict, as you probably know, what’s a trigger for you. What the anxiety provoking situation is. Is it giving a speech? Is it going on a date? You go into your neighbor’s for a barbecue interviewing with your boss, knowing on a subway, getting an MRI. You know, there are many such a diverse range of experience that are triggers for those who suffer from social anxiety disorder.
You said from preclinical trials until entering phase three trials, how long did that take?
This is a different story, because this was initially invented by a brilliant doctor named dr. Lewis Monte based here in Silicon Valley at a company called Ferron pharmaceuticals. And they did a lot of the early developments funded by a family office and the team at Baron and the team at VistaGen have long standing relationships and one case going back about 20 years with our chief medical officer. So in 2016, I got my eye on these two assets, page 94 being pH 10. And we developed a business arrangement that made sense for us to acquire those two assets and bring them into Vista gin pH 94 B and pH 10. So there was a gap in time where is often the case cash strapped, private companies have a fits and starts type of a development program where you get to a phase. If you don’t have the capital, you have to go find the capital and they had some gaps in development. So I guess I would say really the typical hall is about 15 years from bench to bedside. Sometimes it can be faster. Sometimes it can be even longer. I think that kind of will fit on that track here, although we’ve really accelerated quite a bit of the activity since we brought them in house two years ago,
15 years, that’s a long time to be working on one product. I mean, it must be exciting every step of the way. I’m sure it goes by in the blink of an eye when there’s always new results coming out. And as you go through the phases,
A lot of hoops and hurdles, there’s no question you look for go, no go points all along the way. And patient endurance is certainly a necessary trait in this business. It’s not a widget, it’s not a fast and fleeting application that gets a new version every year or every six months. These are businesses that you build and you have protection commercially for quite a long time, once you’re successful. And really they have to have a game changing impact. And even in cases in this business where there isn’t as much white space, as there is here with anxiety, meaning there, isn’t always a case where you just haven’t seen anything new for many decades. And it’s very clear the current standard of care falls short of what people need. And it’s very clear that what you’ve got fundamentally changes, it has the potential to transform that standard of care.
So when you get those opportunities and you have to throw vision into it, of course that’s having vision and raising capital. Those are certainly among the top needs of any CEO in our business, but you have to have the ability to kind of see the fit and you have to look many steps ahead from wherever you are at a decision point to see if that fits going to still be there. What the potential return on the investment is all the different variables. At the end of the day, you’ve got the potential to help a lot of people in an area where the unmet need is tremendous. You’ll find a way to get there and even helping a modest number of people affected with things. It mean there are 40 million people or things in the U S alone, probably more than that now with COVID. Can you imagine if we just, even if a million of those people, let’s say even a hundred thousand of those people turn their lives to the point where they get to be the ideal version of themselves, tremendously innovative group of people now, creative, productive, and it becomes even more incredible.
If that number is 2 million, 5 million, 10 million, 30 million, you know, start to add up global application. And it just becomes such a motivating factor, even on the tough days when you’ve got to grind through whatever the challenge of the day is that driving force, surely that helps all of us in this business keep going. And shareholder value comes on the other side of helping people in biotech. And that’s what I always loved. Still do.
Absolutely. On a global scale of how much you’re going to be helping humans and raising, I guess let’s call it happiness levels across the world. You’re definitely, there’s probably not a lot of companies out there that are going to have as much of an impact. So when does you said from something to bedside, when can we expect bedside? You guys are entering phase three trials. How long has that taken? And so when would phase three trials end and what would happen after phase three trials?
We are really think about it in baseball parlance. If you looked at my office, you’d see it was filled with Willie Mays in baseball parlance. We’re probably, we’ve rounded. Second, we’re headed to third. And when you round third, when you’ve completed your phase three efficacy studies, your pivotal clinical trials, you still have other things you have to put together. And it’s kind of like a college admissions application. You just have all kinds of information that you have to pull together from different perspectives and put that all into an application that hopefully it’s a rolling admission process. And so with us, we have the very first fast track designation from the FDA for the development of pH 94 before social anxiety disorder. Sad. That helps a lot because it allows us to interact with the FDA. And it also eventually will allow us on a rolling basis to submit parts of our NDA.
So the entire package doesn’t have to be reviewed all at once at the very end things can be looked at along the way. And then, then when the final data are done, there’s typically anywhere between eight and 12 months, once you submitted your application for the FDA and other regulatory authorities to get through. So we’ve got a couple more years left, at least in activity. I will start some of that around the middle of next year. We will do the two phase three studies. Those hopefully will be done by the end of 22 and maybe creep into a little bit of 23 with some of the other studies we want to do. We have to do, we don’t have to, but we want to do, for example, a study in benzodiazepine addicts to find out for sure, as we suspect that people will not prefer from an addiction standpoint, the drug over a benzo, one of the key distinguishing features is we think there’s absolutely no basis so far in any study to believe there’s a potential for addiction. So that’s a key distinguishing feature. We’ll talk about in a bit, I would say, um, you know, we’re looking at about three and a half years before we get to the point where we can see the daylight for approval. Hopefully sometime in 23 is when we can get concurrent approval in us. And ideally in China, we just landed a great partnership with the group for key markets in Asia.
It’s really exciting. And I mean, three years this year has gone by in the blink of an eye. So it doesn’t seem like it’s too far away. So let’s get into the juicy stuff. You mentioned benzos. And for those that aren’t super familiar with it, benzos typically Valium and Xanax, which do not have a great reputation are supposed to do the same thing as what you guys are working on your product works in a different way. Can you describe how it works differently? And yeah, let’s just start off with that.
The way benzos work is really well understood. The impact of benzos is understood. The benefits of benzos are understood and the side effects and safety concerns are really well understood as are issues associated with going off of them. And a lot of parallels are until the opioid epidemic. And people have seen a lot of media about that, but the benzo epidemic is certainly finally starting to get some traction. Although the covert pandemic is probably pushed back a little bit on that, given that there seems to be a, an upward, an alarming skyrocketing trend and prescription of benzos. So how do they work? Well, benzos worked very quickly and that’s why people like that’s why doctors prescribed them. And they work in about 30 minutes in most cases. And they go in and they are systemically absorbed trucks. That kind of means that means that they’re oral and they go throughout your body throughout your blood.
And they sort of go on this circulatory loop through the blood, through the liver, through the brain. And that can happen for many hours. Sometimes you can even affect more than a day or two. So there are systemically absorbed drugs that bind to receptors in what are called GABAergic neurons. These are neurons that produce a substance called Gabba located throughout the brain. And those produce widespread increases inhibition, inhibitory GABA function it’s called. So the binding of these receptors throughout the brain results in their side effects, sedation, cognitive impairment, fuzziness, memory loss, eventually over a long period of time, tolerance builds up physical dependence. Do you need more to achieve the same benefit? These are the kinds of concerns and safety issues that are just completely different with pH 94 B because of the way it works. So think of the brain kind of like an electrical circuit court, the way it functions depends on which circuits are turned on and turned off, right?
Which neurons neurotransmissions are inhibited or excited and pH 94 B is, is intra-nasal. It’s not oral, it’s a nasal spray. And it stimulates very short and fast neurocircuits. These are neurotransmissions that convey or send information to a part of the brain called the amygdala. And there, they turn on a switch that release these GABA neurons, which are again, the major inhibitory neurotransmitter in the brain that help to reduce fear and anxiety. The Magdala is the main fear and anxiety center of the brain. So unlike benzos, which are binding to these GABA receptors all throughout the brain, pH 94 B achieves its benefit from a distance, we call it action from a distance. And that