Latest / The BioHub - by Avetix / Episode 166 - Shawn Singh - CEO at Vistagen

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Episode 166 - Shawn Singh - CEO at Vistagen · The BioHub - by Avetix

0:06
Welcome back to the bio Hub. Today we're delighted to welcome
0:10
Sean Singh, the Chief Executive Officer of Vistigen now.
0:15
Sean has LED Vistigen since 2009 and brings more than 30 years of
0:19
experience across biotech, pharma, venture capital and CRO
0:23
leadership. With a career spanning company
0:25
building, strategic growth, and drug development, he brings a
0:29
broad and highly experienced perspective on what it takes to
0:32
advance innovation within CNS. Sean, it's great to have you
0:36
with us today. Ben, it's it's great to be here
0:38
again today. Thank you very much.
0:40
Just again, we're a public company on NASDAQ, so I got to
0:44
upfront give the disclaimer. Please take a look at our SEC
0:49
filings. I'll be giving you some
0:50
forward-looking statements most likely about the way that we
0:53
think our drugs work and their potential.
0:55
So please take a look at the the public filings in the States for
1:00
those of you who are in the states or anywhere.
1:02
But it's great to be here today. I really do appreciate the
1:05
opportunity to have a chat with you.
1:07
Yeah, no worries at all. I guess, you know, to begin with
1:10
Sean, you know, can you just walk us through your career
1:12
path, I mean, the, the transition from law into biotech
1:15
and really the key moments that have shaped how you lead today?
1:19
You know, I, when I, I like the question, but I've gotta say
1:23
upfront, I've really had the the career blessing that many get,
1:27
but in particular here been surrounded by just incredibly
1:31
smart and talented, passionate people throughout all the
1:34
different stages of the career. So and that that fact has really
1:38
opened up countless doors and opportunities throughout What we
1:44
have here in drug development is a very ever changing ecosystem,
1:49
as you know and as your listeners know.
1:51
So around drug discovery, drug development, I've been able to
1:56
have experience in the services that support a lot of what needs
2:01
to be leaned into in order to be successful, beginning with big
2:05
laws, you said in the early 90s. And at the Silicon Valley
2:09
offices of Morrison and Forster, when I was drafting prospectuses
2:13
back then, it really became pretty clear working on IP OS,
2:18
that the emerging biotech sector at that time really was pretty
2:22
easy to develop an affinity for the space.
2:25
And it was fascinated by, you know, a sector that can really
2:30
have not only potential economics, but a value that is
2:34
profoundly potential directed at changing people's lives.
2:38
Right. And then that really got me to
2:42
continue to focus on an industry where your time and your talent
2:46
can contribute to something, you know, larger than yourself.
2:50
And that the rinse and repeat opportunity in, in the
2:53
ecosystem, whether it's with the CRO like keto research venture
2:57
firm like Keto Bioventures or ultimately currently like in
3:00
Vistogen. And, and I think that continues
3:03
to fascinate today, especially as we see, you know, AI coming
3:06
in and making a difference for efficiency.
3:09
Yeah, exactly. I mean, over the last 30 years
3:11
or so, the the landscape within biotech has changed and shifted
3:15
so much. And you know, as you mentioned,
3:16
you know, AI is going to be a real catalyst for for future
3:19
innovation. So it's going to be interesting
3:21
to see how things change over the next 30 as well.
3:23
Yeah, it's not for the faint of heart, that's for sure.
3:25
There's a lot of fits and starts.
3:27
Capital is so critical at all different times.
3:30
Geopolitics comes into play, national politics comes into
3:34
play. And so we've seen so many
3:36
different cycles over the few decades.
3:38
But you know, sitting here in South San Francisco in the birth
3:42
place of biotech, I can tell you we're continually surrounded by
3:46
growth and innovation. And it's as exciting now, if not
3:50
more so really than it's ever been.
3:52
And I think that's that's what keeps people coming in every day
3:56
and, and yeah, moving forward. Talk to me a bit about Visigen
4:01
then. I mean, what, what was it
4:02
specifically about Visigen that really made you believe there
4:05
was an opportunity to build something genuinely
4:08
differentiated here? Yeah, it's never really one
4:12
thing, but it's always grounded in science.
4:16
It's grounded ultimately later in data.
4:18
But it would initially drew me to visogen was stem cell
4:20
technology, believe it or not way back when an investment we
4:24
had made when I was running the buy side fund Keto Bioventures,
4:28
but also neuroscience and the fascination around neuroscience
4:32
continues today with the with the class of fairings that we've
4:36
got that we think are highly differentiated and really at a
4:40
leading edge of the way we can give patients agency to deal
4:44
with a lot of different disorders.
4:46
But I think it's, you know, it's the opportunity to really deploy
4:51
energy in scientific lanes that you can see potentially have a
4:58
difference to flip what is really a suboptimal standard of
5:02
care at any particular time. And that changes as people and
5:07
we as a civilization go through a different level of journey.
5:11
No one anticipated some of the things we've had to innovate
5:14
around rapidly A COVID, for example.
5:17
But you know, you have cases where people are often waiting
5:22
in silence. And I think here with
5:24
neuropsychiatric disorders in particular, certainly up until
5:28
the pandemic and and since then, if you could see a silver lining
5:32
in the pandemic, it was really that it's OK to not be OK.
5:36
And people are talking more about getting assistance.
5:38
And there's an ecosystem built up with telehealth mental
5:41
health. But I think again, back at the
5:44
fundamental point of your question, which was having the
5:47
opportunity to develop and deliver treatments that not only
5:54
are effective, but align with the way that people live and how
6:00
they seek care today. And at visiting, we're really
6:03
trying to meet people where they are.
6:05
Yeah. And obviously you know, social
6:07
anxiety disorder is a is a heavy focus for you guys and and it's
6:10
often under appreciated as a major unmet need.
6:14
Why do you feel that, you know, sort of SAD has become such an
6:18
important focus for Vistogen? It's massively under
6:22
appreciated, no question in the States alone here, and I keep
6:27
saying this days because I know you're over in London, even with
6:29
the sunny day behind you, which you typically don't see.
6:32
But here we have over 30 million adults in the US that are
6:36
affected with social anxiety disorder and and it's just it's
6:40
so much more than shyness. It's the way that it's
6:44
characterized by profound fear and anxiety about being judged
6:48
or humiliated or embarrassed in what many would consider normal
6:54
social and performance situations.
6:57
So that especially if it's team orientation in the workplace or
7:02
at school or any social relationship.
7:05
But the, the, the impact on the daily life of people that go
7:12
through this journey, which the onset begins typically in
7:14
adolescence and the mean duration is a couple of decades.
7:18
And so as people go through different seasons in their
7:21
journey, different types of stressors impair or impact the
7:25
way that they're able to to function.
7:29
And so to be able to try to unpack some of the ways people
7:35
have built their entire lives around avoidance and away from
7:40
engagement and the opportunities that are associated with
7:43
engagement in many contexts, social or vocational or
7:47
academic, that's what we're trying to deal with.
7:50
And so the, you know, it's, it's just a, it's a disorder that's
7:55
so pervasive, but at the same time, often people suffer in
8:00
silence about it. And so we're trying to raise
8:03
awareness at the same time provide an opportunity for what
8:08
really we haven't seen an approval in social anxiety is
8:10
sort of the FDA in a couple of decades, never for the acute
8:14
treatment of social anxiety. So giving someone with a
8:18
mechanism of action and that's how you build your development
8:21
programs is around the way you think the drug works.
8:24
Commonly not telling anything surprising to the audience on
8:27
that. But here we've got rapid onset
8:30
potential with this mechanism of action across the faring
8:33
platform that allows people, we believe and we've seen it and
8:38
reported open label studies to have agency over how they can
8:42
tailor to fit the use of a medication in this arena.
8:45
In particular to knock down the the anxiety, the overactive
8:51
amygdala that causes them to avoid and not engage and to be
8:56
fearful and anxious about how they might be judged or
9:00
humiliated or embarrassed in in these situations.
9:03
Yeah. I, I think the impact of it is,
9:06
is definitely understated. I mean, it can be devastating to
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people both, as you mentioned, from a, from a social
9:11
perspective, but, but also when it comes to work.
9:14
So I think it's, it's definitely an area that that, like you
9:17
mentioned, is under appreciated. And you know, the work that
9:20
you're doing can hopefully, hopefully help resolve that.
9:23
You know, more so since the, like I said, since the pandemic,
9:26
we've seen prevalence continue to increase.
9:28
There's unfortunately that's the case.
9:31
You know, the main driver, social media has a major impact,
9:35
unfortunately, to increase the incidence and prevalence of this
9:38
disorder, but so does team orientation.
9:42
So in the workplace, now that people are back to work, back to
9:47
school, we're starting to see some of the same trends that we
9:50
saw before the pandemic. And the sad part too, is it
9:54
there's often a match set starting with anxiety, moving to
9:59
depression, moving to suicidal ideation and suicidality,
10:03
especially in, in the younger populations, you know, the
10:07
demographics sort of 18 to 25 or so.
10:11
And, and that's, you know, that's concerning because the,
10:15
the opportunity to lean into current medications, it's, it's
10:19
suboptimal. Benzodiazepines drugs, you know,
10:23
that cause cognitive impairment, cause a risk of abuse liability,
10:27
cause the kinds of things that don't people aren't comfortable
10:32
when they have to work and interact if they have existing
10:36
classes of medications on board and the antidepressants, for
10:40
example, you're going to get the typical side effects and safety
10:44
concerns regardless of whether it's helping you in the moment.
10:47
So that's what we're trying to knock down our our lead drug
10:50
candidates called fasadenol in phase three development and
10:54
that's an acute fairing acute treatment as a, a nasal spray
10:59
that is an investigational medicine again in late stage
11:02
development. So that's what we're trying to
11:04
bring to to the party. Yeah.
11:07
And and you're taking, you know, a very different approach from
11:09
traditional CNS drug development.
11:11
I mean how? How would you explain the
11:13
intranasal neurocircuitry model in simple?
11:16
Terms, simple terms often challenging for the non side.
11:23
You know, I think I think of it as using the nose as a portal to
11:27
regions of the brain that definitely impact different
11:31
disorders and different conditions.
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And so the faring platform, all of those drug candidates, all
11:38
five of them are focused on nose to brain neurocircuitry.
11:42
But doing that in a non systemic in a way that you don't have to
11:46
take a pill and drive the drug all the way through your body,
11:49
through your blood, across the blood brain barrier to try to
11:53
get to and activate certain neurological activity, but avoid
11:59
others, right? So you don't want to the typical
12:02
pinball game in the brain when a drug will go to where you want
12:05
it to go at the same time it goes off target, causing
12:08
significant side effects and safety concerns.
12:10
All farines are administered as intranasal or nasal sprays
12:14
because the receptors of the neurons we need to activate or
12:18
only in the nasal passage. And so with low microgram
12:22
levels, we're spraying directly onto the receptors of the
12:25
neurons that we need to activate chemosensory neurons that then
12:29
sort of project like a relay to what are called the olfactory
12:34
bulbs at the base of the brain and then from there to different
12:37
regions of the brain depending upon the objective.
12:40
So for anti anxiety effects, we're trying to knock down the
12:44
activity of the amygdala and but don't do that in a way like say
12:49
a benzodiazepine would do where you're flooding the zone with,
12:54
with GABA, you want to be able to activate GABA related
12:58
activity, but not increase the supply.
13:01
In the case of menopausal hot flashes, for example, we're
13:05
driving that neuro circuitry to a different part of the brain,
13:09
the hypothalamus that's sort of the the body's thermostat.
13:13
And So what we've seen in data there, similar to what we saw in
13:18
in social anxiety disorder was that the patient with agency was
13:22
able to knock down the number and the frequency and severity
13:26
of hot flashes in menopausal women.
13:30
Yeah, I mean, and that, that is absolutely fascinating,
13:33
especially to people who are, you know, slightly detached from
13:35
the industry, the the the likes of myself who aren't operating
13:38
in these sort of environments day in, day out as you are.
13:41
The fact that a, a, a sort of, you know, nasal spray can have
13:45
that much involvement within the neurons within the brain is, it
13:48
is, you know, it's extraordinary.
13:50
Well, if you think of the disorder it is, it is just
13:54
extraordinary in that ultimately, again, you're trying
13:57
to meet the patient where they are.
13:59
And a lot of the the stressful situations are predictable.
14:04
Some aren't predictable. You know, if you got to go in
14:07
the tube is instead of your your black cab, then you're going to
14:10
be maybe worried about that. If you know you've got a date or
14:15
you've got an interview or you've got to give a
14:17
presentation to your colleagues, again, that's predictable.
14:20
And the safety profile is, is exquisite.
14:23
All that we've seen so far, which is what we look at really
14:27
early on. Is it possible to give people
14:30
that kind of on demand agency? So in our studies, people can
14:35
take it up to six times a day because you may have different
14:37
stressors in the morning when you wake up and who you're
14:40
seeing at lunch and you going to your in laws for dinner.
14:43
You know, whatever it is that is throughout the course of your
14:45
day. And some days you don't have
14:48
anything. So you don't want a medication
14:49
on board in your body when you don't have a need for it.
14:53
If you're out by a pond reading a book, that's not going to be a
14:57
case where you want an old school antidepressant in your
15:01
body not helping you, but maybe causing some side effects and
15:05
safety concerns. So again, trying to figure out,
15:08
you know, early on, is there potential to to amplify
15:14
favorably the way people live their lives and what we've found
15:18
with intranasal drugs and neurocircuitry based.
15:21
And you don't have to drive a drug through your whole body.
15:24
You don't have drug interaction. You're not worried about, you
15:27
know, the the liver being affected by too much drug
15:30
hanging out in there. You're not worried about.
15:33
We know these drugs don't bind in the brain to opiate,
15:37
nicotine, dopamine abuse liability receptors.
15:39
So you're staying away from the stay aways at the same time give
15:42
an agency. And, and you know, throughout
15:45
your development, you know, Visigen now has five assets with
15:49
positive data in humans. I mean, what what does that
15:52
really tell you about the strength and the potential of
15:54
the platform that you have? Well, it gives us tremendous
15:57
confidence in the potential of this new class of medications.
16:01
It's not always easy to raise awareness, but again, data
16:05
drives it, science drives it. And so when you have multiple,
16:09
we have it's a very diverse pipeline around different
16:13
indications that are affected by different regions of the brain.
16:18
So to be able to drive non systemically, not through the
16:23
whole body, drive it from a low microgram level dose that's
16:27
about 3 inches from the brain. That's why you get rapid onset.
16:30
We see onset super fast. And as a result, Fasidinol for
16:35
social anxiety disorder. Rifisolone is our drug candidate
16:39
for menopausal hot flashes, which again the the treatment
16:45
alternatives are are not great for millions and millions of
16:49
women that are affected by menopausal hot flashes across
16:53
the world. Itruvone is our drug candidate
16:56
for major depressive disorder that again, these are all at
17:00
least in phase two. Thesodinols had positive phase
17:03
three as well as a couple of setbacks.
17:06
PH-15 is for cognitive impairment associated with
17:11
mental fatigue. So you know, sleep shift
17:15
workers, nurses, people, truck drivers, people that don't want
17:19
to take high dose caffeine or any other kind of stimulant.
17:23
And then PH284 earlier in the pipeline is for is for cachexia,
17:30
cancer cachexia in this case where again a different part of
17:32
the brain associated with appetite in a population that
17:36
sometimes struggles, especially late stage cancer patients with
17:40
nutrition. So it's really, it's a
17:43
fascinating platform given the flexibility and diversity now
17:49
backed by a heck of a lot of science that's associated with
17:52
its potential. Yeah.
17:54
But but obviously, you know, this isn't a typical CNS model
17:57
where you can rely on standard animal PK or brain exposure
18:01
assumptions. I mean, how does that really
18:03
change the way that you think about development?
18:07
Yeah, you have to find workarounds.
18:08
I mean that's with anything. You got to have a kind of a
18:11
constellation of a flexibility here again, when when the PK
18:16
chapter isn't going to apply because we're not able to detect
18:20
any of these drugs in plasma. We've done other ways of going
18:24
at selecting dose through in vitro work with calcium flux,
18:30
with nasal cells that we harvest from human subjects and look at
18:34
whether there's calcium flux. We'll move from there to
18:37
electrophysiology where subjects will come in, in a Phase 1
18:41
context and we will insert electrodes in, in on their nose.
18:46
And with different formulations we we are able to see how fast
18:50
there is a depolarization effect.
18:53
Same thing with the olfactory bulbs.
18:55
We're able to see, you know really how rapidly we're seeing
19:00
onset and directional activity to different regions of the
19:04
brain. So going at it a little bit
19:06
differently with some of the the the biomarkers that we look at
19:12
and the assays that we use that fit for this class of drugs.
19:17
Yeah. And I guess from, from, from my
19:20
side, from a more selfish perspective, you know, when,
19:23
when you are going at it with, with such a different method,
19:27
how, how does that impact your hiring?
19:29
I mean, you, you must need to build an outstanding team to be
19:32
able to think outside the box and, and really come up with
19:35
these creative ways to to move development forward.
19:38
Well, for us, fortunately, we have really the, the, I believe
19:41
the pioneer in this space with Doctor Lewis Monti to me ought
19:45
to win a Nobel Prize downstream because to be able to deal with
19:49
some of these disorders without worrying about every other
19:54
medication that somebody has to take for the rest of what their
19:57
issues are. It's it's transformative.
19:59
So around Doctor Monty and his decades of experience, we've
20:04
been able to build the kind of scientific.
20:08
Team you need you have to perhaps you have to have not
20:12
only a creative mind but also people that can actually execute
20:17
on those ideas. As we've seen over decades now
20:20
with Doctor Monty's work before joining us and and since he's
20:23
been with us for the last six years.
20:26
Yeah, I. Mean what?
20:28
When a mechanism doesn't fit, you know what What would be
20:30
classed as the typical biotech playbook?
20:33
What in your opinion, really matters most when building
20:36
conviction? Is it the clinical data, is it
20:39
the regulatory strategy or or is it just how clearly you you're
20:42
able to tell the story? You know when when, like I
20:46
noted, when people have old friend ways, including
20:50
regulators like why is it? Tell us why this isn't a benzo?
20:55
Tell us why this isn't an antidepressant?
20:57
Rebut all the presumptions for every analogue that's known to
21:01
either industry or the regulatory authorities.
21:04
It takes an it takes a different level of effort, but it does
21:10
build a conviction around innovation.
21:12
It, again, it requires a constellation of behaviors and
21:16
flexibilities that, I mean, I would say it's a lot like we're
21:20
seeing right now with AI these days around the integration of
21:25
AI into drug discovery, into drug development, into all kinds
21:28
of sectors. Yeah, you know, there's a,
21:30
there's a learning curve, but at a minimum, the science and the
21:33
data have to be the bedrock of driving confidence and
21:37
conviction and the regulatory strategy and advocacy, no
21:40
question. I mean, clearly articulating any
21:44
database differentiation to multiple audience audiences is a
21:50
critical art. And again, you need, it's, it's
21:53
a team sport. You need a lot of folks around
21:56
you to be able to build that, that database bedrock.
22:00
But at the same time, you know, it's trying to it's access and
22:05
it's constantly trying to patiently but relentlessly build
22:12
awareness around why the differentiation makes sense.
22:17
You know, when we have conversations and people will
22:20
see the aggregate safety data that we have in a particular
22:24
indication, there's certainly skepticism upfront because no
22:30
neuropsychiatric drug candidate has delivered that kind of a of
22:35
a situation where, you know, the most prevalent treatment
22:40
emerging adverse effect. We've seen more than 5% this
22:43
headache transient, nothing more than 5% else in the largest
22:47
study we reported so far. But once we get to explain the
22:51
mechanism, often there are these epiphany eyes where, oh, OK, now
22:54
we get it. You're not driving the drug
22:56
through the body. It's not going into the brain.
22:58
It's, you know, so again, it's trying to patiently walk
23:02
through, you know, with an order of administration that allows
23:05
that understanding and awareness to settle in.
23:08
And then rinse and repeat, rinse and repeat, rinse and repeat.
23:12
No matter how many times and places you get to do it, you do
23:16
it the same way. Does that differ at all in in an
23:19
investor context? I mean, when you're building the
23:22
right syndicate to be backing you, is there anything else that
23:24
that's particularly important? We have to have every other part
23:28
of the puzzle. You have to understand what's
23:30
the need. You have to understand why is it
23:33
their, their competitive advantage, all the basics as to
23:37
what's the cost and the timing to get there, all the different
23:41
components that support a business case, because it always
23:45
has to start with the business case.
23:47
And ultimately, you know, you're driving it.
23:49
What's the return you can get on anything that you want to put at
23:51
risk. We're not in a business to
23:54
eliminate risk. That's impossible.
23:57
We've got to assess what risks make sense to take given the
24:01
potential for that return to, to come forward.
24:05
But again, it's the same thing. It's, it's just like every other
24:08
industry except here, there's longer runways on the other
24:11
side. If you're right to generate that
24:15
economic benefit. It's not like you're going to
24:17
have a widget sneak up on you in a minute.
24:20
And fundamentally early on, that's what moved me towards
24:22
biotech versus tech because I was doing tech IPOs at the same
24:26
time frame and, you know, getting a return based on a lot
24:31
of investment and a lot of risk that has to be taken.
24:34
Web development is it is a long runway to get to do something
24:40
that actually can end up helping people, and it takes
24:43
perseverance. No matter what you do, you've
24:45
got to always get up instead of giving up.
24:49
Yeah, Most most certainly. I mean, just to sort of wrap,
24:52
wrap things up here, Sean, you know our typical final question,
24:56
if you could have dinner with any scientist or innovator, past
24:59
or present, who would it be and why?
25:03
Well, I get the good fortune of having dinner with Doctor Monty,
25:05
so. But no, seriously, that is
25:10
serious. But gosh, there's so many to
25:12
choose from. Maybe, maybe Sir Alexander
25:18
Fleming, I would say, you know, I know he's Scottish and you're
25:23
in England, but that's OK. I just think it that that the
25:29
discovery of penicillin and his contributions to kicking off the
25:32
antibiotic revolution. If you think about how many
25:35
lives have been saved, including my own in the context of, you
25:41
know, the use of antibiotics. So probably him, you know,
25:43
there's I always wonder what keeps, you know, what kept in
25:47
his case, what kept driving and driving to have the thought to
25:51
do what initially he did. And then a couple of a decade or
25:54
so later, I think he ended up getting Co Nobel Prize with a
26:00
couple of others a decade or so after that.
26:02
But that'd be just one. There's many others, but that's
26:06
what comes to mind. I don't know why but.
26:09
It would, it would certainly be be fascinating.
26:11
I mean, when you when you get to have the opportunity to have
26:14
have dinner with Doctor Monty every so often, the the next
26:16
guest has to be pretty spectacular.
26:18
Yeah. Exactly.
26:21
Well, it's been, it's been an absolute pleasure having you on
26:23
with me today. Sean.
26:25
I really appreciate you joining me.
26:27
Yeah, well, likewise anytime. Happy to do it.
26:29
Yeah, I certainly appreciate that.
26:31
And thank you to everybody for watching.
26:33
Yeah, stay tuned, make sure you like and subscribe.
26:35
There'll be plenty more episodes on the way.
26:37
Cheers. Goodbye.