June 28, 2024 • 23 mins
**UPDATE** Since this episode was recorded, Takeda announced the results of the phase 3 soticlestat trials, which did not meet their primary endpoints.
We welcome Dr. Toshiya Nishi and Jason Tardio from Ovid Therapeutics. Dr. Nishi, with over 20 years of experience in drug discovery, discusses his role in the development of soticlestat and ongoing research on KCC2 activators for neurological disorders. Jason Tardio, Ovid's COO, shares insights on the company's focus on rare neurological disorders, including epilepsy, and its strategic initiatives for advancing treatments. Listen to their inspiring journey from the inception of Ovid Therapeutics to its current breakthroughs, and their perspectives on fostering a quality-driven and risk-tolerant culture in drug development.
https://ovidrx.com/
00:00 Introduction and Welcome
00:40 Meet the Guests: Dr. Toshiya Nishi and Jason Tardia
02:04 The Journey of Ovid Therapeutics
03:58 Discovering Saticklistat: A Serendipitous Breakthrough
08:35 Strategic Initiatives and Future Directions
13:48 Collaboration and Culture at Ovid Therapeutics
17:38 Ensuring Quality in Drug Development
21:50 Personal Insights and Closing Remarks
24:07 Conclusion and Farewell
Qualio website:
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Previous episodes:
https://www.qualio.com/from-lab-to-launch-podcast
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https://forms.gle/uUH2YtCFxJHrVGeL8
Music by keldez
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:01):
Hi there! Welcome to the FromLab to Launch podcast by Qualio,
where we share inspiring storiesfrom the people on the front
lines of life sciences.
Tune in and leave inspired tobring your life saving products
to the world.
Meg Sinclair (00:18):
Hi everyone.
And thank you for tuning in tofrom lab to launch podcast
brought to you by Qualio.
I'm Meg, your host, and I'mdelighted to be here with you
today.
Before we dive into today'sepisode, we'd love it if you
could take a moment to rate andshare the podcast with your
circle of science enthusiasts.
And if you're interested inbeing a guest on the show,
please check out the applicationin the show notes.
(00:40):
Today, we're excited to bejoined by two distinguished
guests from Ovid Therapeutics.
First, we have Dr.
Toshiya Nishi.
A veterinarian by training withover 20 years of experience in
drug discovery and translationalresearch at Takeda
Pharmaceutical, Tashia played apivotal role in the discovery
https (00:56):
otter.
ai So it's a stat, a drug codeveloped with Ovid
Therapeutics.
Now as the Senior Director ofDrug Discovery at Ovid, he's
spearheading research on KCC2activators, aiming to develop
innovative treatments forneurological disorders.
Sorry, Meg.
I'm going to jump in and be therude PR person.
(01:18):
Um, it's, it's Saticklistat.
Saticklist.
It's almost like tickle.
Saticklistat.
Saticklistat.
Okay.
So I don't know if you want todo that piece over again.
Okay.
Ticlistat.
Yeah, I can start from thatsentence.
Dr.
Nishi played a pivotal role inthe discovery of Ticlistat, a
drug co developed with OvidTherapeutics.
(01:38):
Now as a senior director of drugdiscovery at Ovid, he's
spearheading research on KCC2activators, aiming to develop
innovative treatments forneurological disorders.
Also joining us is Jason Tardia,the Chief Operating Officer of
Ovid Therapeutics.
He has over two decades ofexperience in the
biopharmaceutical industry,including leading with multiple
(02:01):
sclerosis franchise at Novartis.
We'll get into the inspiringstory of Ovid Therapeutics, a
company dedicated to creatinglife changing medicines for
patients with rare neurologicaldisorders.
We'll discuss their journey frominception to launch and
advancing the field ofneuropharmacology.
So let's get started.
Welcome to the show, Jason andTashia.
(02:22):
for
Toshiya Nishi (02:22):
having me.
Great.
Can
Meg Sinclair (02:25):
you tell us a little bit more about how the
two of you got connected and thestory behind Ovid Therapeutics?
Jason Tardio (02:32):
Sure, I, I, I'll start.
Um, uh, so Ovid's Therapeuticshas been around since 2014.
So it's nearly a journey of 10years as a company.
And the company, uh, wasfounded, uh, with a mission to
dive into neurological, uh,research.
At this time, Meg, I think it'simportant to understand 10 years
(02:54):
ago, many companies wereactually running away and
divesting a number of theirneuroscience programs.
And so the founder of thecompany, a gentleman by the name
of, of Matt during, uh, soughtand saw an opportunity, uh, for
a company like Avid to actuallypivot towards, uh, neuroscience
and specifically, uh, rareconditions, uh, of the brain.
(03:16):
And so, uh, thus, uh, he, heformed a company initially
around a medicine calledGaboxadol that he enlicensed,
uh, from a company calledLundbeck.
Uh, and the premise for thatspecific medicine.
was that potential impact on anumber of rare
neurodevelopmental disorders.
And so that product was, was,uh, studied in conditions like
(03:39):
Angelman syndrome and fragile Xsyndrome as well.
Um, during his time, uh, of, of,of starting this company, he was
also looking to expand anddiversify the pipeline.
And, and, uh, he had, uh,relationships with a number of
the key R and D executives atTakeda, uh, and through a
meeting with Takeda.
Um, he understood they had adiscussion about a medicine
(04:02):
called saticklostat, uh, thatcertainly Toshia can tell you a
little bit more about, but amedicine that had been studied
in a variety of differentpreclinical animal models within
neuroscience, uh, andAlzheimer's, for example, and
other conditions.
Uh, and in some of these models,there was some clear signals
about the potential for thismedicine to be.
(04:24):
an anti seizure medicine.
It was suppressing seizures thatwould normally erupt in some of
these animal models,specifically animal models of
Alzheimer's.
And so Takeda had an idea thatthis could be a nice anti
seizure approach.
They tested the medicine in anumber of, uh, animal models of
epilepsy, specifically Gervaissyndrome, and it seemed to work,
(04:47):
but they did not have at thattime epilepsy experience.
They didn't have rare neurologyexperience, and so it could have
been just a serendipitousmeeting of the two because Ovid
was at this company focused onrare neurological disorders.
Takeda had this asset that theybelieved could work in some of
these rare epilepsies, butdidn't quite know the approach
to take, uh, and lo and behold,a relationship, uh, was, was
(05:10):
started.
Meg Sinclair (05:12):
That's an amazing journey.
Toshe, you played a criticalrole in the discovery and
development of ceticlistat.
What was it like to discover thepotential?
that it holds and how did thatmoment of realization feel for
you as a scientist?
Toshiya Nishi (05:25):
Yeah, as Jason, Jason mentioned, it's a total
serendipity, but first andforemost, uh, let me, let me,
uh, note that, um, all thediscovery works for Sotiklis
that was done together while Iwas There that, that should be,
uh, noted.
Yeah.
Uh, first, uh, first, uh, firfirst of all, I, I, I would like
(05:46):
to explain briefly about Cletaon its own.
Uh, I'm, I'm, uh, tongue.
I'm, I know by my tongue alittle bit though.
It is a small molecule inhibitorof enzyme called, uh,
cholesterol 24 Hydroxy.
Uh, another complicated name,though.
It's an enzyme, you know,explicitly.
Uh, um.
(06:07):
It's expressing the brain, uh,you know, playing a role for
regulation of a cholesterolmetabolism in the brain, but
this enzyme was not studiedextensively as a drug target for
many, many years ago.
So, in a way, just discovery ofsorticular set, uh, you know,
small molecule inhibitor on itsown is, is actually a
(06:29):
serendipity.
Um, uh, Uh, we then published apaper back in 2020 from the
journal Scientific Report.
Uh, we described how we ended upwith, um, the discovery of anti
epileptic property of, uh,Ceticlacet.
Uh, that was, uh, that was aquite a bit of, uh, serendipity.
(06:52):
As, as described in the paper,uh, So Tickle Asset was
initially, uh, evaluated in ananimal model of Alzheimer's
disease.
It was not a seizure model, butinterestingly, uh, this animal
model, I mean, it was a mousemodel.
Animals die suddenly, uh, inprematurity.
(07:13):
I mean, it's a sudden death, soyou never see, you never see,
uh, how they die.
But, you know, I was lucky orunlucky enough to see, uh,
encounter a couple of momentsof, uh, animal death.
Uh, and, you know, theyapparently die of seizure.
And, uh, uh, actually I, I look,I looked up the literature and
this particular, uh, uh, mousemodel Alzheimer's disease is
(07:36):
known for a high mortality rate.
And lo and behold, weserendipitously realized that,
uh, solace treated, uh, youknow, animals had a few cases
of, uh, you know, uh, you know,death and, uh, survival benefit.
So that led us to a hypothesisof that.
Uh, so Solace has a potential.
(07:59):
Uh, to be a seizure medicationprotecting, uh, animals from,
uh, dying from seizure, uh, thatled us to the, uh, you know,
series of, uh, studies, um, ofCE in a whole bunch of
different, uh, seizure seizuremodels.
And that, that, that study wasalready published from, uh,
journal epilepsy in 20, uh, 20.
(08:19):
So, yeah, it's a, so Teta is,uh, you know, product of many,
many Serre deities.
Meg Sinclair (08:26):
It is.
It sounds very serendipitous,the journey to you two meeting
together and, um, Stiklostatcoming to be a treatment for
epilepsy.
Um, for Jason, given yourbackground in the industry, what
strategic initiatives at OvidTherapeutics have you found most
particularly impactful inadvancing treatments for
neurological disorders?
Jason Tardio (08:47):
Yeah, well, I can tell you what drew me to Ovid
Therapeutics.
Uh, I was Drawn to the companybecause it has a clear focus on
patients, uh, and patientsliving with, at the time, you
know, rare, uh, orphan relatedspecific conditions, patients
that had no pharmacologicaloptions.
Um, And so for me, that missionaround trying to find and bring
(09:13):
some hope to these families andthese individuals living with
these conditions again in whichthey had nothing, um, spoke to
my heart.
And so that that's what drew meto to the company.
Um, you know, avid.
still has a very clear focus ondeveloping medicines of high end
needs, specifically inepilepsies and other seizure
related disorders.
(09:34):
Uh, but we also have a vision ofexpanding beyond that into,
into, you know, more generalbrain conditions as well.
And so the story in my fiveyears here has evolved, as I
mentioned, When I first started,we were clearly, uh, in, uh, a
rare neurodevelopmentaldisordered company, uh, and in
parallel, we had this program,Ceticlastat, through a
(09:55):
partnership with Takeda, and wewere developing medicine for a
number of rare epilepsies ordevelopmental and epileptic
encephalopathies.
Since then, we've evolved, uh,as a lot of companies do, uh,
and, uh, expanded our breath abit.
So, again, we still have a clearfocus on, on epilepsies, uh, but
(10:16):
we've, uh, broadened ourpipeline to largely focus on a
number of small molecule, um,best in class first in class
therapies that focus on a wholerange of conditions.
Our most advanced program is adrug called OV888, uh, slash
GV101.
This is a highly selective ROK2inhibitor, uh, through a
(10:38):
collaboration with a companycalled Graviton.
We had identified a conditioncalled cerebral cavernous
malformations.
This is a condition that affectsUpwards of 1.
5 million individuals in theUnited States, they develop
these raspberry like lesionswithin the central nervous
system.
Uh, and these lesions cause awhole host of symptoms,
(11:01):
everything from seizures, whichis why we got cancer.
condition, but also headache,leg and arm weakness, etc.
But also there's a very severerisk of these lesions, uh,
hemorrhaging or bleeding.
And if they do so, they cancause a whole host of downstream
consequences.
There's no approved therapiesfor this respective condition.
(11:22):
Uh, and there's good biologicalrationale and good animal model
data to support that.
A highly selective rock toinhibitor like OV888 slash GV101
could have benefit.
And so we're finishing a phaseone for that respective asset,
and we'll be announcing thoseresults in the first half of
this year in the next month orso.
(11:43):
And we hope to move that into aphase two program later this
year.
Beyond that, we also have aprogram that's in phase one,
ov329, which is a nextgeneration GABA
immunotransferase inhibitor.
This is a validated approach toepilepsy.
There's a first generationmedicine called Vagabatrin
that's quite effective in anumber of refractory epilepsies,
(12:04):
but it comes with, uh, an oculartoxicity signal.
About 30 percent of patientsdevelop, uh, visual field
deficits.
And so we believe our moleculeof E3 to 9, a much more potent
GABAminotransferase inhibitor,uh, could be dosed, uh,
potentially, uh, at a much lowerdose.
You might not see some of theaccumulation you see with the
(12:25):
GABAtrin, and therefore we mightbe able to eliminate this ocular
toxicity or adverse event.
We're finishing up a phase onein the oral formulation of that,
and we're also moving forward inIV formulation.
We'll file an IND this year andhope to move that into a phase
one program next year for statusepilepticus.
(12:45):
And then behind that, as Toshiamentioned, we have, and he's
working very diligently on alibrary of compounds that are
direct activators of thepotassium.
Chloride cotrans, cotransporter2 or KCC2 channel, which is a
channel specifically located inthe central nervous system.
This channel is implicatedacross a variety of conditions,
everything from rare conditionslike Rett syndrome, certainly
(13:07):
epilepsies, but also evenpotentially more broad
conditions like, uh,schizophrenia and psychosis.
And so we believe we're the onlycompany activators of this
channel.
We'll file a first IND laterthis year in the most advanced
compound, which is a drug calledOV329.
Uh, and hope to get that intohumans next year.
So we've advanced our thinking,but we're still a company at our
(13:29):
core that focuses on patients,as I've mentioned, focuses on
conditions of high unmet need.
Uh, and we're really excitedabout the programs that we're
bringing forward.
Meg Sinclair (13:39):
I'm really excited to see all the things that you
guys are pushing out andaccomplishing this year.
It sounds like a lot of excitingnews coming out of it this year.
That's great.
It's a unique opportunity tohave you both here on the show
together in a perfect world.
How should someone in anoperations role and a drug
development or scientist rolework together?
Toshiya Nishi (13:58):
Yeah, absolutely.
Yeah.
I mean, as Jason introduced me,I am now spearheading, uh, you
know, just drug discovery andpreclinical development of KACC
to activate a program.
Uh, it's such an importantprotein, uh, regulating a
fundamental mechanism of ourbrain.
(14:19):
So, I mean, we are envisioningapplication of KCC to activate,
uh, to a wide spectrum of braindiseases, uh, as, as he
mentioned.
Fundamentally, I mean, mydiscipline is pharmacology,
which means identification andmaximization of the therapeutic
values of drug candidates, whichis really, really interesting.
(14:42):
I mean, I, I, As you, uh,introduced me, uh, I am a
veterinarian by training.
Uh, so this is where my, youknow, uh, background as a
veterinarian plays a role.
Uh, in the veterinarian sciencecourse, you need to learn a lot
of things.
I mean, uh, many diseases andincluding even, uh, parasitosis,
(15:04):
even a fish disease, all sortsof things, um, pathology and
histology.
Uh, that way, I mean, uh, we Youknow, I tend to, maybe I tend to
see brain diseases slightly, uh,from a different perspective
from other, uh, you know, uh,authentic neuro,
neuropharmacologist.
Uh, interestingly, in thisindustry, um, uh, most, most of
(15:28):
the veterinarians, uh, Walk as atalk is called this, uh, but you
know, I'm, I would strongly, youknow, recommend, um, you know, a
firm cozy as a, as a careeropportunity for a veterinarian.
Now we, we, we do have our ownadvantage to, to, uh, to
contribute to, um, drugdevelopment.
Jason Tardio (15:47):
Absolutely.
And Meg, what I would add thereis, you know, look, we're a
small company at AvidTherapeutics.
We're roughly 50 employees, giveor take, and so whether we like
it or not, we're forced to worktogether very closely across all
functions, and my role as theChief Operating Officer, my job
in a very simplistic form is toensure that the company operates
(16:08):
at an efficient level across allfunctions on a daily basis, that
all of us are collectivelymarching towards the goal.
Uh, accomplishment of the goalsand objectives that the company
has set forward.
Uh, and so when we think aboutkind of Toshia and, and what he
does, uh, and his team, and howsome of my functions interact, I
mean, clearly, uh, Toshia isdriving a lot of our, our early
(16:30):
research, but even early on inresearch and development, you
need to be thinking about Theend game, right?
What is the ultimate goal?
What is the condition that wecould and potentially may want
to address with these with theseassets?
Um, what's the opportunity?
Um, what's that path?
Uh, and and as you do this, youneed a lot of insight and input
(16:51):
across the variety of thefunctions of the organization.
For example, The commercialfunction reports into me.
And so one of the things youalways have to ask is, all
right, well, what's what wouldbe the commercial opportunity if
we brought this drug into X, Y,Z condition on everything goes
smooth and we get this topatients, you know, what is that
(17:12):
opportunity here?
What does that return on thatinvestment look like?
And so you need to startthinking about these things
early on.
And so as a small company, youknow, we do work very closely
together.
And I think that's one of thePositive attributes of a company
like Avid is that because we'resmall, we're agile, we're
flexible, but everyone is veryclose.
And we, you know, we drivetowards a similar goal
Meg Sinclair (17:38):
on that note of working all together and driving
for that same goal here atqualia.
We provide an EQS softwarecompanies for life science
companies like yourself.
So quality is near and dear toour hearts and mine, especially
as our quality manager.
So I like to ask executives, um,and scientists, as you're
developing drugs to bring tomarket for patients, how are you
(17:59):
ensuring a quality of culture onyour teams?
Jason Tardio (18:04):
A quality of culture?
Yes.
Yeah.
Quality of culture.
Yeah.
Well, look, I, I mean, cultureshould be embedded in a company.
It should be in woven into thefabric of what a company does
day in and day out.
Um, and so.
You know, culture can be definedas a lot of different things.
The way that I personally defineit, and then I'd love to hear
(18:25):
Toshia's thoughts on this is,um, you know, culture is what is
what you feel when you walkthrough the doors of an
organization, right?
How does, uh, the vibe of thecompany feel?
How do people, as we've justdiscussed, collaborate and work
together.
How does how do people supportone another?
One of the things in the biotechindustry is you take risks, you
(18:48):
take calculated risks.
Those risks more times than notdon't work.
How are we supporting oneanother?
And, you know, extending a handto pick someone up when maybe
their experiment didn't work,but, you know, we give them a
good pat on the back and say,look, what can we learn from
this as we move forward?
That's what culture is allabout.
Uh, and it, it also goes back alittle bit to, one of the things
(19:10):
I mentioned about what, whatattracted me to Avid
Therapeutics, you know, patientcentricity, I think is a key
part of culture as well.
I mean, look, we'd be naive ifwe said here, and said that we,
you know, we're, we're a non forprofit.
We are a for profit entity.
We're a publicly traded company.
So there is a business aspect towhat we do, but I've always
(19:30):
believed that if you put thepatient first, you put the needs
of the patient first, you driveforward drug development and
then subsequentcommercialization.
with a specific laser focus andwhat's in the best interest of
the communities that you'regoing to serve, that the
business and the profits willfollow.
And so I think all of these arecomponents of culture.
I hope that answers yourquestion.
Toshiya, I'm sure you havethoughts.
Toshiya Nishi (19:51):
Yeah, absolutely.
To me, I mean, as an R& Dorganization, uh, everything is
down to risk tolerance.
I mean, drug discovery, drugdevelopment is innately very,
very difficult.
But, uh, what we have as a, uh,what we should have a culture
(20:12):
component to be successfulorganization.
It's a, it's a, you know, a goodbalance of risk tolerance.
Uh, indeed, I mean, in orbit,uh, corporate culture, we have a
couple of properties.
I would like to point out, becourageous.
And be curious.
I mean, these two arefundamentally important culture
(20:34):
woven into the organization oforbit.
Without that, I mean, we areoften intimidated of doing,
doing new things.
I mean, Especially in my, in my,uh, uh, responsibility, I am
working on, uh, you know, um,drops with new mechanism action,
uh, which, which is quitechallenging.
(20:56):
Uh, but all of it certainly has,uh, uh, you know, uh, culture of
encouraging to, uh, to not beafraid of risk.
And of course we need toconsider the risk and benefit
balance, but this organizationhas a right set of mindset, you
know, driving R& D, which isinnately, uh, you know, high
(21:17):
risk.
Uh, that, that's, yeah, that,that is exactly, I wanted to
come to all of it.
This philosophy has beenactually inherited from the
founder of Orbit, uh, uh, asJason pointed out, who is Mark
Turing, who is super, supercourageous.
Uh, he was a fearless person,and he still remains an
(21:37):
important role model.
Uh, it's eternal role model inmy, in my mind.
Meg Sinclair (21:43):
That's great.
I love that.
Be curious and be courageous.
That's great advice, Toshiya.
Um, well, our last question ismore of a fun one.
We like to ask each of ourguests, if we ran into you at
the bookstore at your locallibrary, in which section would
I find each of you?
Jason Tardio (21:58):
Ooh, Toshiya, do you want to go first?
Toshiya Nishi (22:02):
I, I like social science.
I, I'm a scientist and I know, Imean, I like economics, uh, I
actually, uh, subscribes to the,the economist, um, you know, I,
I tend to see, you know, uh,anything happening in, in this
world, uh, from a scientificperspective.
(22:25):
I want to understand why this ishappening.
Uh, what is driving this?
I mean, I'm not, you know, uh,I'm not a social scientist, but,
uh, I always enjoy view, uh, allof, you know, difficult things
happening today.
But, uh, I always want tounderstand what is behind this.
So, for that reason, I, I reallylove social science.
Probably you, you will find methere.
Meg Sinclair (22:47):
Perpetually curious.
Yeah,
Jason Tardio (22:49):
for me, Meg, I definitely skew more nonfiction
than fiction and if I had to gothrough subcategories and I had
to pick one, it'd probably bebiographies.
I love learning about people,their journey, how they've
gotten to where they're at, thestruggles they've had in life,
how they've overcome those.
Uh, yeah, I'm certainly 100percent nonfiction versus
fiction, uh, biographies, otherhistorical accounts of, of
(23:12):
events.
I just, I love learning abouthistory and people.
Meg Sinclair (23:16):
Always good lessons to learn from history.
Well, thank you so much forsharing that little personal,
uh, bit and your story at Ovid,thank you so much again for
joining us and where can thosewho want to follow along with
your journey, find you andconnect.
Toshiya Nishi (23:30):
It's my pleasure.
Thank you.
Meg Sinclair (23:32):
Yeah.
Jason Tardio (23:33):
Uh, so yeah, so for me, uh, yeah, obviously our
website for, from a companyperspective is, uh, uh, www.
ovidrx.
com, uh, and you can find me onLinkedIn at Jason Tardio, T A R
D I O.
Meg Sinclair (23:49):
Great.
Thanks Jason.
Jason Tardio (23:50):
Great.
Thank you.
Thank you both.
Thank you.
Bye now.
Bye.
Thank you for listening to thisweek's episode of From Lab to
Launch, brought to you byQualio.
(24:12):
If you like what you've heard,please subscribe and give the
show a positive review.
It really helps us out.
For more information aboutQualio, our guest today, or to
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Until next time.
Hi there! Welcome to the FromLab to Launch podcast by Qualio,
where we share inspiring storiesfrom the people on the front
lines of life sciences.
Tune in and leave inspired tobring your life saving products
to the world.
Meg Sinclair (00:18):
Hi everyone.
And thank you for tuning in tofrom lab to launch podcast
brought to you by Qualio.
I'm Meg, your host, and I'mdelighted to be here with you
today.
Before we dive into today'sepisode, we'd love it if you
could take a moment to rate andshare the podcast with your
circle of science enthusiasts.
And if you're interested inbeing a guest on the show,
please check out the applicationin the show notes.
(00:40):
Today, we're excited to bejoined by two distinguished
guests from Ovid Therapeutics.
First, we have Dr.
Toshiya Nishi.
A veterinarian by training withover 20 years of experience in
drug discovery and translationalresearch at Takeda
Pharmaceutical, Tashia played apivotal role in the discovery
https (00:56):
otter.
ai So it's a stat, a drug codeveloped with Ovid
Therapeutics.
Now as the Senior Director ofDrug Discovery at Ovid, he's
spearheading research on KCC2activators, aiming to develop
innovative treatments forneurological disorders.
Sorry, Meg.
I'm going to jump in and be therude PR person.
(01:18):
Um, it's, it's Saticklistat.
Saticklist.
It's almost like tickle.
Saticklistat.
Saticklistat.
Okay.
So I don't know if you want todo that piece over again.
Okay.
Ticlistat.
Yeah, I can start from thatsentence.
Dr.
Nishi played a pivotal role inthe discovery of Ticlistat, a
drug co developed with OvidTherapeutics.
(01:38):
Now as a senior director of drugdiscovery at Ovid, he's
spearheading research on KCC2activators, aiming to develop
innovative treatments forneurological disorders.
Also joining us is Jason Tardia,the Chief Operating Officer of
Ovid Therapeutics.
He has over two decades ofexperience in the
biopharmaceutical industry,including leading with multiple
(02:01):
sclerosis franchise at Novartis.
We'll get into the inspiringstory of Ovid Therapeutics, a
company dedicated to creatinglife changing medicines for
patients with rare neurologicaldisorders.
We'll discuss their journey frominception to launch and
advancing the field ofneuropharmacology.
So let's get started.
Welcome to the show, Jason andTashia.
(02:22):
for
Toshiya Nishi (02:22):
having me.
Great.
Can
Meg Sinclair (02:25):
you tell us a little bit more about how the
two of you got connected and thestory behind Ovid Therapeutics?
Jason Tardio (02:32):
Sure, I, I, I'll start.
Um, uh, so Ovid's Therapeuticshas been around since 2014.
So it's nearly a journey of 10years as a company.
And the company, uh, wasfounded, uh, with a mission to
dive into neurological, uh,research.
At this time, Meg, I think it'simportant to understand 10 years
(02:54):
ago, many companies wereactually running away and
divesting a number of theirneuroscience programs.
And so the founder of thecompany, a gentleman by the name
of, of Matt during, uh, soughtand saw an opportunity, uh, for
a company like Avid to actuallypivot towards, uh, neuroscience
and specifically, uh, rareconditions, uh, of the brain.
(03:16):
And so, uh, thus, uh, he, heformed a company initially
around a medicine calledGaboxadol that he enlicensed,
uh, from a company calledLundbeck.
Uh, and the premise for thatspecific medicine.
was that potential impact on anumber of rare
neurodevelopmental disorders.
And so that product was, was,uh, studied in conditions like
(03:39):
Angelman syndrome and fragile Xsyndrome as well.
Um, during his time, uh, of, of,of starting this company, he was
also looking to expand anddiversify the pipeline.
And, and, uh, he had, uh,relationships with a number of
the key R and D executives atTakeda, uh, and through a
meeting with Takeda.
Um, he understood they had adiscussion about a medicine
(04:02):
called saticklostat, uh, thatcertainly Toshia can tell you a
little bit more about, but amedicine that had been studied
in a variety of differentpreclinical animal models within
neuroscience, uh, andAlzheimer's, for example, and
other conditions.
Uh, and in some of these models,there was some clear signals
about the potential for thismedicine to be.
(04:24):
an anti seizure medicine.
It was suppressing seizures thatwould normally erupt in some of
these animal models,specifically animal models of
Alzheimer's.
And so Takeda had an idea thatthis could be a nice anti
seizure approach.
They tested the medicine in anumber of, uh, animal models of
epilepsy, specifically Gervaissyndrome, and it seemed to work,
(04:47):
but they did not have at thattime epilepsy experience.
They didn't have rare neurologyexperience, and so it could have
been just a serendipitousmeeting of the two because Ovid
was at this company focused onrare neurological disorders.
Takeda had this asset that theybelieved could work in some of
these rare epilepsies, butdidn't quite know the approach
to take, uh, and lo and behold,a relationship, uh, was, was
(05:10):
started.
Meg Sinclair (05:12):
That's an amazing journey.
Toshe, you played a criticalrole in the discovery and
development of ceticlistat.
What was it like to discover thepotential?
that it holds and how did thatmoment of realization feel for
you as a scientist?
Toshiya Nishi (05:25):
Yeah, as Jason, Jason mentioned, it's a total
serendipity, but first andforemost, uh, let me, let me,
uh, note that, um, all thediscovery works for Sotiklis
that was done together while Iwas There that, that should be,
uh, noted.
Yeah.
Uh, first, uh, first, uh, firfirst of all, I, I, I would like
(05:46):
to explain briefly about Cletaon its own.
Uh, I'm, I'm, uh, tongue.
I'm, I know by my tongue alittle bit though.
It is a small molecule inhibitorof enzyme called, uh,
cholesterol 24 Hydroxy.
Uh, another complicated name,though.
It's an enzyme, you know,explicitly.
Uh, um.
(06:07):
It's expressing the brain, uh,you know, playing a role for
regulation of a cholesterolmetabolism in the brain, but
this enzyme was not studiedextensively as a drug target for
many, many years ago.
So, in a way, just discovery ofsorticular set, uh, you know,
small molecule inhibitor on itsown is, is actually a
(06:29):
serendipity.
Um, uh, Uh, we then published apaper back in 2020 from the
journal Scientific Report.
Uh, we described how we ended upwith, um, the discovery of anti
epileptic property of, uh,Ceticlacet.
Uh, that was, uh, that was aquite a bit of, uh, serendipity.
(06:52):
As, as described in the paper,uh, So Tickle Asset was
initially, uh, evaluated in ananimal model of Alzheimer's
disease.
It was not a seizure model, butinterestingly, uh, this animal
model, I mean, it was a mousemodel.
Animals die suddenly, uh, inprematurity.
(07:13):
I mean, it's a sudden death, soyou never see, you never see,
uh, how they die.
But, you know, I was lucky orunlucky enough to see, uh,
encounter a couple of momentsof, uh, animal death.
Uh, and, you know, theyapparently die of seizure.
And, uh, uh, actually I, I look,I looked up the literature and
this particular, uh, uh, mousemodel Alzheimer's disease is
(07:36):
known for a high mortality rate.
And lo and behold, weserendipitously realized that,
uh, solace treated, uh, youknow, animals had a few cases
of, uh, you know, uh, you know,death and, uh, survival benefit.
So that led us to a hypothesisof that.
Uh, so Solace has a potential.
(07:59):
Uh, to be a seizure medicationprotecting, uh, animals from,
uh, dying from seizure, uh, thatled us to the, uh, you know,
series of, uh, studies, um, ofCE in a whole bunch of
different, uh, seizure seizuremodels.
And that, that, that study wasalready published from, uh,
journal epilepsy in 20, uh, 20.
(08:19):
So, yeah, it's a, so Teta is,uh, you know, product of many,
many Serre deities.
Meg Sinclair (08:26):
It is.
It sounds very serendipitous,the journey to you two meeting
together and, um, Stiklostatcoming to be a treatment for
epilepsy.
Um, for Jason, given yourbackground in the industry, what
strategic initiatives at OvidTherapeutics have you found most
particularly impactful inadvancing treatments for
neurological disorders?
Jason Tardio (08:47):
Yeah, well, I can tell you what drew me to Ovid
Therapeutics.
Uh, I was Drawn to the companybecause it has a clear focus on
patients, uh, and patientsliving with, at the time, you
know, rare, uh, orphan relatedspecific conditions, patients
that had no pharmacologicaloptions.
Um, And so for me, that missionaround trying to find and bring
(09:13):
some hope to these families andthese individuals living with
these conditions again in whichthey had nothing, um, spoke to
my heart.
And so that that's what drew meto to the company.
Um, you know, avid.
still has a very clear focus ondeveloping medicines of high end
needs, specifically inepilepsies and other seizure
related disorders.
(09:34):
Uh, but we also have a vision ofexpanding beyond that into,
into, you know, more generalbrain conditions as well.
And so the story in my fiveyears here has evolved, as I
mentioned, When I first started,we were clearly, uh, in, uh, a
rare neurodevelopmentaldisordered company, uh, and in
parallel, we had this program,Ceticlastat, through a
(09:55):
partnership with Takeda, and wewere developing medicine for a
number of rare epilepsies ordevelopmental and epileptic
encephalopathies.
Since then, we've evolved, uh,as a lot of companies do, uh,
and, uh, expanded our breath abit.
So, again, we still have a clearfocus on, on epilepsies, uh, but
(10:16):
we've, uh, broadened ourpipeline to largely focus on a
number of small molecule, um,best in class first in class
therapies that focus on a wholerange of conditions.
Our most advanced program is adrug called OV888, uh, slash
GV101.
This is a highly selective ROK2inhibitor, uh, through a
(10:38):
collaboration with a companycalled Graviton.
We had identified a conditioncalled cerebral cavernous
malformations.
This is a condition that affectsUpwards of 1.
5 million individuals in theUnited States, they develop
these raspberry like lesionswithin the central nervous
system.
Uh, and these lesions cause awhole host of symptoms,
(11:01):
everything from seizures, whichis why we got cancer.
condition, but also headache,leg and arm weakness, etc.
But also there's a very severerisk of these lesions, uh,
hemorrhaging or bleeding.
And if they do so, they cancause a whole host of downstream
consequences.
There's no approved therapiesfor this respective condition.
(11:22):
Uh, and there's good biologicalrationale and good animal model
data to support that.
A highly selective rock toinhibitor like OV888 slash GV101
could have benefit.
And so we're finishing a phaseone for that respective asset,
and we'll be announcing thoseresults in the first half of
this year in the next month orso.
(11:43):
And we hope to move that into aphase two program later this
year.
Beyond that, we also have aprogram that's in phase one,
ov329, which is a nextgeneration GABA
immunotransferase inhibitor.
This is a validated approach toepilepsy.
There's a first generationmedicine called Vagabatrin
that's quite effective in anumber of refractory epilepsies,
(12:04):
but it comes with, uh, an oculartoxicity signal.
About 30 percent of patientsdevelop, uh, visual field
deficits.
And so we believe our moleculeof E3 to 9, a much more potent
GABAminotransferase inhibitor,uh, could be dosed, uh,
potentially, uh, at a much lowerdose.
You might not see some of theaccumulation you see with the
(12:25):
GABAtrin, and therefore we mightbe able to eliminate this ocular
toxicity or adverse event.
We're finishing up a phase onein the oral formulation of that,
and we're also moving forward inIV formulation.
We'll file an IND this year andhope to move that into a phase
one program next year for statusepilepticus.
(12:45):
And then behind that, as Toshiamentioned, we have, and he's
working very diligently on alibrary of compounds that are
direct activators of thepotassium.
Chloride cotrans, cotransporter2 or KCC2 channel, which is a
channel specifically located inthe central nervous system.
This channel is implicatedacross a variety of conditions,
everything from rare conditionslike Rett syndrome, certainly
(13:07):
epilepsies, but also evenpotentially more broad
conditions like, uh,schizophrenia and psychosis.
And so we believe we're the onlycompany activators of this
channel.
We'll file a first IND laterthis year in the most advanced
compound, which is a drug calledOV329.
Uh, and hope to get that intohumans next year.
So we've advanced our thinking,but we're still a company at our
(13:29):
core that focuses on patients,as I've mentioned, focuses on
conditions of high unmet need.
Uh, and we're really excitedabout the programs that we're
bringing forward.
Meg Sinclair (13:39):
I'm really excited to see all the things that you
guys are pushing out andaccomplishing this year.
It sounds like a lot of excitingnews coming out of it this year.
That's great.
It's a unique opportunity tohave you both here on the show
together in a perfect world.
How should someone in anoperations role and a drug
development or scientist rolework together?
Toshiya Nishi (13:58):
Yeah, absolutely.
Yeah.
I mean, as Jason introduced me,I am now spearheading, uh, you
know, just drug discovery andpreclinical development of KACC
to activate a program.
Uh, it's such an importantprotein, uh, regulating a
fundamental mechanism of ourbrain.
(14:19):
So, I mean, we are envisioningapplication of KCC to activate,
uh, to a wide spectrum of braindiseases, uh, as, as he
mentioned.
Fundamentally, I mean, mydiscipline is pharmacology,
which means identification andmaximization of the therapeutic
values of drug candidates, whichis really, really interesting.
(14:42):
I mean, I, I, As you, uh,introduced me, uh, I am a
veterinarian by training.
Uh, so this is where my, youknow, uh, background as a
veterinarian plays a role.
Uh, in the veterinarian sciencecourse, you need to learn a lot
of things.
I mean, uh, many diseases andincluding even, uh, parasitosis,
(15:04):
even a fish disease, all sortsof things, um, pathology and
histology.
Uh, that way, I mean, uh, we Youknow, I tend to, maybe I tend to
see brain diseases slightly, uh,from a different perspective
from other, uh, you know, uh,authentic neuro,
neuropharmacologist.
Uh, interestingly, in thisindustry, um, uh, most, most of
(15:28):
the veterinarians, uh, Walk as atalk is called this, uh, but you
know, I'm, I would strongly, youknow, recommend, um, you know, a
firm cozy as a, as a careeropportunity for a veterinarian.
Now we, we, we do have our ownadvantage to, to, uh, to
contribute to, um, drugdevelopment.
Jason Tardio (15:47):
Absolutely.
And Meg, what I would add thereis, you know, look, we're a
small company at AvidTherapeutics.
We're roughly 50 employees, giveor take, and so whether we like
it or not, we're forced to worktogether very closely across all
functions, and my role as theChief Operating Officer, my job
in a very simplistic form is toensure that the company operates
(16:08):
at an efficient level across allfunctions on a daily basis, that
all of us are collectivelymarching towards the goal.
Uh, accomplishment of the goalsand objectives that the company
has set forward.
Uh, and so when we think aboutkind of Toshia and, and what he
does, uh, and his team, and howsome of my functions interact, I
mean, clearly, uh, Toshia isdriving a lot of our, our early
(16:30):
research, but even early on inresearch and development, you
need to be thinking about Theend game, right?
What is the ultimate goal?
What is the condition that wecould and potentially may want
to address with these with theseassets?
Um, what's the opportunity?
Um, what's that path?
Uh, and and as you do this, youneed a lot of insight and input
(16:51):
across the variety of thefunctions of the organization.
For example, The commercialfunction reports into me.
And so one of the things youalways have to ask is, all
right, well, what's what wouldbe the commercial opportunity if
we brought this drug into X, Y,Z condition on everything goes
smooth and we get this topatients, you know, what is that
(17:12):
opportunity here?
What does that return on thatinvestment look like?
And so you need to startthinking about these things
early on.
And so as a small company, youknow, we do work very closely
together.
And I think that's one of thePositive attributes of a company
like Avid is that because we'resmall, we're agile, we're
flexible, but everyone is veryclose.
And we, you know, we drivetowards a similar goal
Meg Sinclair (17:38):
on that note of working all together and driving
for that same goal here atqualia.
We provide an EQS softwarecompanies for life science
companies like yourself.
So quality is near and dear toour hearts and mine, especially
as our quality manager.
So I like to ask executives, um,and scientists, as you're
developing drugs to bring tomarket for patients, how are you
(17:59):
ensuring a quality of culture onyour teams?
Jason Tardio (18:04):
A quality of culture?
Yes.
Yeah.
Quality of culture.
Yeah.
Well, look, I, I mean, cultureshould be embedded in a company.
It should be in woven into thefabric of what a company does
day in and day out.
Um, and so.
You know, culture can be definedas a lot of different things.
The way that I personally defineit, and then I'd love to hear
(18:25):
Toshia's thoughts on this is,um, you know, culture is what is
what you feel when you walkthrough the doors of an
organization, right?
How does, uh, the vibe of thecompany feel?
How do people, as we've justdiscussed, collaborate and work
together.
How does how do people supportone another?
One of the things in the biotechindustry is you take risks, you
(18:48):
take calculated risks.
Those risks more times than notdon't work.
How are we supporting oneanother?
And, you know, extending a handto pick someone up when maybe
their experiment didn't work,but, you know, we give them a
good pat on the back and say,look, what can we learn from
this as we move forward?
That's what culture is allabout.
Uh, and it, it also goes back alittle bit to, one of the things
(19:10):
I mentioned about what, whatattracted me to Avid
Therapeutics, you know, patientcentricity, I think is a key
part of culture as well.
I mean, look, we'd be naive ifwe said here, and said that we,
you know, we're, we're a non forprofit.
We are a for profit entity.
We're a publicly traded company.
So there is a business aspect towhat we do, but I've always
(19:30):
believed that if you put thepatient first, you put the needs
of the patient first, you driveforward drug development and
then subsequentcommercialization.
with a specific laser focus andwhat's in the best interest of
the communities that you'regoing to serve, that the
business and the profits willfollow.
And so I think all of these arecomponents of culture.
I hope that answers yourquestion.
Toshiya, I'm sure you havethoughts.
Toshiya Nishi (19:51):
Yeah, absolutely.
To me, I mean, as an R& Dorganization, uh, everything is
down to risk tolerance.
I mean, drug discovery, drugdevelopment is innately very,
very difficult.
But, uh, what we have as a, uh,what we should have a culture
(20:12):
component to be successfulorganization.
It's a, it's a, you know, a goodbalance of risk tolerance.
Uh, indeed, I mean, in orbit,uh, corporate culture, we have a
couple of properties.
I would like to point out, becourageous.
And be curious.
I mean, these two arefundamentally important culture
(20:34):
woven into the organization oforbit.
Without that, I mean, we areoften intimidated of doing,
doing new things.
I mean, Especially in my, in my,uh, uh, responsibility, I am
working on, uh, you know, um,drops with new mechanism action,
uh, which, which is quitechallenging.
(20:56):
Uh, but all of it certainly has,uh, uh, you know, uh, culture of
encouraging to, uh, to not beafraid of risk.
And of course we need toconsider the risk and benefit
balance, but this organizationhas a right set of mindset, you
know, driving R& D, which isinnately, uh, you know, high
(21:17):
risk.
Uh, that, that's, yeah, that,that is exactly, I wanted to
come to all of it.
This philosophy has beenactually inherited from the
founder of Orbit, uh, uh, asJason pointed out, who is Mark
Turing, who is super, supercourageous.
Uh, he was a fearless person,and he still remains an
(21:37):
important role model.
Uh, it's eternal role model inmy, in my mind.
Meg Sinclair (21:43):
That's great.
I love that.
Be curious and be courageous.
That's great advice, Toshiya.
Um, well, our last question ismore of a fun one.
We like to ask each of ourguests, if we ran into you at
the bookstore at your locallibrary, in which section would
I find each of you?
Jason Tardio (21:58):
Ooh, Toshiya, do you want to go first?
Toshiya Nishi (22:02):
I, I like social science.
I, I'm a scientist and I know, Imean, I like economics, uh, I
actually, uh, subscribes to the,the economist, um, you know, I,
I tend to see, you know, uh,anything happening in, in this
world, uh, from a scientificperspective.
(22:25):
I want to understand why this ishappening.
Uh, what is driving this?
I mean, I'm not, you know, uh,I'm not a social scientist, but,
uh, I always enjoy view, uh, allof, you know, difficult things
happening today.
But, uh, I always want tounderstand what is behind this.
So, for that reason, I, I reallylove social science.
Probably you, you will find methere.
Meg Sinclair (22:47):
Perpetually curious.
Yeah,
Jason Tardio (22:49):
for me, Meg, I definitely skew more nonfiction
than fiction and if I had to gothrough subcategories and I had
to pick one, it'd probably bebiographies.
I love learning about people,their journey, how they've
gotten to where they're at, thestruggles they've had in life,
how they've overcome those.
Uh, yeah, I'm certainly 100percent nonfiction versus
fiction, uh, biographies, otherhistorical accounts of, of
(23:12):
events.
I just, I love learning abouthistory and people.
Meg Sinclair (23:16):
Always good lessons to learn from history.
Well, thank you so much forsharing that little personal,
uh, bit and your story at Ovid,thank you so much again for
joining us and where can thosewho want to follow along with
your journey, find you andconnect.
Toshiya Nishi (23:30):
It's my pleasure.
Thank you.
Meg Sinclair (23:32):
Yeah.
Jason Tardio (23:33):
Uh, so yeah, so for me, uh, yeah, obviously our
website for, from a companyperspective is, uh, uh, www.
ovidrx.
com, uh, and you can find me onLinkedIn at Jason Tardio, T A R
D I O.
Meg Sinclair (23:49):
Great.
Thanks Jason.
Jason Tardio (23:50):
Great.
Thank you.
Thank you both.
Thank you.
Bye now.
Bye.
Thank you for listening to thisweek's episode of From Lab to
Launch, brought to you byQualio.
(24:12):
If you like what you've heard,please subscribe and give the
show a positive review.
It really helps us out.
For more information aboutQualio, our guest today, or to
be a guest on a future episode,please refer to the show notes.
Until next time.
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