Prof Craig Ritchie: Looking Back at EPAD, moving forward in Alzheimer's Disease

Judith: Welcome to Berry's In the
Interim podcast, where we explore the

cutting edge of innovative clinical
trial design for the pharmaceutical and

medical industries, and so much more.

Let's dive in.

Scott Berry: All right.

Welcome everybody.

Back to In the interim, uh, I'm your
host Scott Berry, and I have a really

special guest, a cool guest with me today,
professor Craig Richie, who is the founder

and CEO of Scottish Brain Sciences.

He's also a professor of brain
health and neurodegenerative

diseases at the University of St.

Andrews, formerly University of Edinburgh.

And Craig will help if it's Edinburgh.

Edinburgh.

I'm, I'm a

US person.

Edinburgh.

Edinburgh.

Uh, and, and interestingly for
today's discussion, he was the

chief investigator of EPA d and so
that'll be one of our topics today.

So welcome to in the interim, Craig.

Craig Ritchie: Thanks Scott.

It's delighted to be here.

Thanks for the invitation.

Scott Berry: Yeah, so let's talk
about, first, let's jump into EPA D.

So EPA D was the European
Prevention of Alzheimer's dementia.

In IMI funded project from 2015 to

Craig Ritchie: Yeah.

Scott Berry: Uh, uh, for, for full
disclosure, Barry consultants and

I personally was involved in EPA in
the, the statistical engine room as

we referred to it on trial design.

So tell me about, a little bit about,
introduce to our audience, epa.

Craig Ritchie: Sure.

So, yeah, I mean, I think there's,
there's, there's lots of, um, ways

I could introduce the project, but I
think that the, the most important was.

That it was, it was trying to really
address a major problem that we, we

had then to a fair degree we still
have, and that is to, to really

accelerate the development of new
therapies for Alzheimer's disease.

Um, and there was a whole bunch of reasons
back in 2015 when we started the project

that we felt there was challenges in
developing new therapies and EPA was.

Hugely ambitious project that really did
in many ways, tried to boil the ocean.

You know, we, we wanted
to look at recruitment.

We wanted to look at early
detection of the disease.

We wanted to look at new trial
designs, which of course you

are intimately involved with.

Um, and huge program of
research across Europe and with

partners all over the world.

Um, just to give it a sense of scale,
I think at one point there were.

Over 400 people working on the project.

It was a 64 million euro funded program.

Um, and 39 partners from pharmaceutical
companies, small medium enterprises,

as well as, um, as, as as major
academic institutions across Europe.

So yeah, huge, a huge program
and like I said, trying to really

help develop more rapidly, better
therapies for Alzheimer's disease.

Scott Berry: Okay, so there, there,
in, in my view, and, and you'll help

me with this, but two major parts
to this, two major innovations.

was the intent to build a platform

Craig Ritchie: Mm-hmm.

Scott Berry: Have a common master
protocol, a platform trial, bring

multiple therapies on, can share
the infrastructure, share control,

arms accelerate development.

That was a, a, a huge part of the project.

The second was the readiness cohort,

Craig Ritchie: Mm-hmm.

Scott Berry: we're involved in a number
of platform trials, and we'll sort of get

to that in this, this sort of before 2020.

Craig Ritchie: Mm-hmm.

Scott Berry: trial and, and then COVID
hit and, and, and what we understood

about platform trials after this
and the weird place EPA was, but

the readiness cohort is something
I've never seen in a platform trial.

Craig Ritchie: Yeah.

Scott Berry: explain the readiness
cohort and its relationship.

I, I know it has a huge amount
of scientific benefit outside

of the platform trial, but

Craig Ritchie: Hmm.

Scott Berry: it called a readiness cohort?

Craig Ritchie: Yeah, I mean, it, it,
it, it, it, one of the major problems

that we had, and it's, I think it's
probably true of a lot of clinical

trials and a lot of clinical areas,
was how long it takes to identify

people who are eligible for the trial.

And that's often the case because,
you know, a trial starts the sponsor.

You know, creates the
inclusion exclusion criteria.

They fire the gun and it's as if it's as,
it's as if it's the first trial that's

ever been done, and you're starting, every
time you do a new trial, it's like you're

starting from, from, from baseline again.

So the readiness cohort was, was,
was, uh, a very good, um, uh,

program that created readiness.

You, you had thousands of research
participants who were ready to

be involved in a clinical trial.

And the readiness was probably in some
ways across two, sort of, you know, um,

main, main, main dimensions, if you like.

Number one was they, as people were ready.

So when they were consented into the
cohort study, um, it was very much, this

is the intention of the cohort study
is if you're eligible and you're, and

you're willing to participate, there
could and should be a drug trial for you.

You at some point in the
not too distant future.

So they were adjusted, they were
psychologically ready, they were

committed to being in a drug trial.

And then the other element
of readiness was we knew a

lot about these participants.

We knew their amyloid status, we knew
their cognitive status, we knew their

medical comorbidities so that when
the trial started or when the trial

would've started, we would have a very
low screen failure rate because we

weren't, you know, again, just going
to the community and hoping we picked

up a bunch of people with Alzheimer's.

Pathology or particular range.

So that was, that was the two major,
major dimensions of, of readiness.

But like you said, Scott, there was,
there was other things came outta that

data set, um, that we were, we were, we
were collecting, which are, you know,

been actually transformative in terms
of our understanding of early disease.

'cause one of the, the key things,
like you said at the, of the, of

the, of the, at the beginning,
this was the European prevent

prevention of Alzheimer's dementia.

So nobody in that cohort had a
dementia syndrome at baseline.

These were people who were maybe at
high risk of developing the dementia

syndrome but didn't actually have it.

So this was very much about the
earliest stages of the disease and,

and, and exactly where people I
think want to be treated, you know,

before the symptoms start to emerge.

Scott Berry: Okay.

And, and the scale of this,
uh, uh, to the, this cohort.

So these are individuals,
I think it was 50 and older

Craig Ritchie: Yeah.

Scott Berry: may have risk factors.

Um, they, they don't have a, a,
a, a diagnosis of Alzheimer's.

There's some level of risk at it.

I think at some point
there were 2000 patients

Craig Ritchie: Just over 2000.

Yeah.

Yeah.

Scott Berry: as part of this cohort.

30 centers around Europe

Craig Ritchie: Hmm.

Scott Berry: longitudinally you'd follow
the, the, the participants in the cohort.

And one, one role of this is when there's
a drug in the platform trial, you can

now go to these participants, you know so
much about them that the screen failure

rate at that point may be very, very low.

Craig Ritchie: Yeah.

Scott Berry: Contrasted to if a
sponsor goes out and they want

to find participants that have, a
pathological amyloid or biomarkers

consistent with the cognitive part,

Craig Ritchie: Yeah,

Scott Berry: get 90% screen failure.

Craig Ritchie: totally.

Yeah.

Scott Berry: cost in this.

So this, this was a huge advance
for companies that wanted to come

into the platform, and largely
this was incredibly successful.

So the readiness cohort
was incredibly successful.

Craig Ritchie: Yeah.

I mean, it was, it was in, and I think
what we did was in, in, in the first

year of the program was, was, you
know, bring together investigators,

um, companies, sponsors, you know,
mainly their sort of r and d division.

And set out the, the
framework for the program.

But also there was a lot of hearts
and minds that we were winning about

the need for this in, in, in the area
that we were, we were all committed

to, and namely the Alzheimer's space.

Um, I mean, it was a hu I mean it was in
many ways a hugely successful project.

Um, um, not just for developing
that cohort study, which I think

is the largest, um, collection
of data and participants.

Uh, still to date, uh, with the, the
depth and the level of phenotyping.

Um, one thing we didn't mention
was, of course, that everybody, for

instance, had spinal fluid taken
an all very detailed brain imaging.

So this wasn't, there were certainly
elements of this, which were, um,

necessary for, for finding people
for trials, but we also had this

kind of secondary objective of, you
know, really trying to understand

the, the upstream disease mechanism.

That drive, um, Alzheimer's disease
and, you know, with, with a view

eventually, I guess, to going even further
upstream with, um, with interventions

and precision medicine ultimately
around particular individuals in

particular, you know, profiles of, of,
of disease well before symptoms develop.

So, and a lot of the objectives
of vpa, if you, if you like, have

survived into a lot of programs today.

You know, 'cause I think the,
the, the, the gang we had together

of academics and industry folks
was second to none globally.

I mean, there was just the, the thought
leaders, the, the passion that was in the

program, the early career researchers,
it was, it was incredible legacy

that our projects had moving forward.

Scott Berry: Uh, one, one thing I
remember and it sort of, I think

it's become more common now, 10 years
after, but it was one of the first

times I was really involved where the
participants were such an important

part of the design of the cohort.

Craig Ritchie: Hmm.

Scott Berry: were there at.

At meetings and had a huge impact
in the, in the research, and it was

really my first experience of that.

Craig Ritchie: Yeah.

And, and it was actually interesting
that when we got the original brief from

IMI medicines, I dunno how much people
know about those, those programs, but

the, the more like a tender, you know,
there's actually an objective that's set

out by, by industry, by by European Union
through the NIV Medicines initiative.

Of, and I, I remember one of the
things that we added into the original

tender was, was an additional work
package work package eight, which was

ethics, legal, and social implications.

'cause we did consider that having this
approach, which was novel, you know,

people still probably still think about
Alzheimer's as an older person's disease

that affects, you know, people, you know,
they're say about to, you know, um, you

know, have, have, have problems with
driving or or, or day to day living.

And we are courses.

Investigators and as companies thought,
you know, this is a midlife disease

and this is something that, you know,
affects people before symptoms develop.

So we, we also had to give a lot
of consideration to the narrative

around what we were doing.

So, like you said, we had a system in
place where we had participant panels

at a site level, at a national level.

At international level.

We had also lots of press releases with,
with participants who'd been involved.

So it was a, it was, it was, it was
a, it was a, and we've actually, as

you, as you, as you may recall, we've
actually published some papers on.

Research participants being
involved in design and, and

delivery of the, the program.

So that was a, a huge, um, that stage,
quite innovative, uh, wave forward,

uh, particularly with this population.

Scott Berry: Yeah.

Okay.

So now, uh, the role of the readiness
cohort for a platform trial.

Craig Ritchie: Hmm

Scott Berry: the, we, we built

Craig Ritchie: mm-hmm.

We did.

Scott Berry: built a protocol.

We went to EMA, we got advice.

we built it so that a, a particular
drug could come on board.

It would be an appendix
within the master protocol.

Multiple drugs could come on board.

There's a readiness cohort, so
now the ability to enroll pa uh,

participants who are ready there.

The phenotype, the, the knowledge
of these patients, the trials built,

and looking back, we never enrolled
an arm in the platform trial.

Craig Ritchie: Correct.

Scott Berry: To some extent
that part was a failure of

Craig Ritchie: Yep.

Scott Berry: ePet had a number of
huge successes and learnings, disease

learnings, I'm sure that are still

Craig Ritchie: Yeah.

Scott Berry: but it didn't happen.

Craig Ritchie: Yeah.

Scott Berry: Why didn't it happen?

Craig Ritchie: Well, I think

Scott Berry: I, I have thoughts.

You have thoughts?

Why didn't it happen?

Craig Ritchie: so, I think, I think
the, um, you know, I mean, I, when I

reflect on this at a personal level,
and, and, and, and people often, often

counsel me against this, I, I do say
that EPAD was a great success against

many different sort of parameters, but
ultimately failed because the, the, the

objective, the number one objective of
EPAD was to set up a platform trial.

Um.

So all the other adjacencies, the cohort
study that, you know, we had this ePad

Academy of early career researchers.

We had a panel, we had the
disease modeling, et cetera.

Ultimately, this, this didn't
meet its primary objective.

Um, and I think, you know, the, the,
the, the, the reasons for that, and

I think we've obviously reflected
on this since 2020, um, were that

I think it was a big leap, if I can
be candid for a lot of the sponsors.

To say we trust this platform for how
we're gonna develop our new therapy.

Because in many ways, we were asking
companies to put in their prized

asset, and particularly a biotech,
for instance, or even a big pharma,

to outsource this in a, in a sense,
to a third party to run the study.

And I think if, if, and you know,
you and I have talked about this

a lot, obviously over the years.

I think if we could have our
time again, it may have been.

Um, useful to sort of put in a repurposed
drug as a proof of proof of platform,

because I think once we had the data that
showed the platform worked the readiness

cohort recruited, well then I think this
sort of created the momentum, uh, and

the, and the, and the assurance that
I think people upstairs in these drug

companies that we weren't necessarily
talking to directly would've had that.

They said, yeah, let's go for it.

We were also a little bit unlucky
that there were a couple of companies,

and I probably shouldn't say who they
were because I'm pretty sure it's

confidential, but who were gonna,
were very committed, but they actually

had problems with phase in phase
one with toxicity and another thing.

So we seemed to have a series of
issues that seemed to work against

us to actually, um, get a drug in.

But I mean, fundamentally, I believe,
I think a lot of people did this is

this is actually the way forward.

Um, and.

Of course 2020 hit, uh, COVID happened
and I think a lot of momentum behind the

project got, got, got lost a little bit.

Um, I think if, if COVID hadn't hit
and we hadn't lost that couple of

years, then I think we would probably
dusted ourselves down regrouped

and gone again a lot more quickly.

Um, but you know, as you know, I'm
trying to, I'm trying to re re-engineer

these things again through channel.

Scott Berry: Yep, I,
so we'll come to that.

So there, there's this idea that
a pharmaceutical company has a

compound and I, I think we saw
examples and we won't mention any

Craig Ritchie: Yeah.

Scott Berry: they saw we could go
into this platform trial that hasn't

enrolled a patient yet, and largely
would be run by CRO, would be,

Craig Ritchie: Hmm.

Scott Berry: their baby to somebody else

Craig Ritchie: Yeah.

Scott Berry: it, but the
numbers lined up well.

Craig Ritchie: Yeah.

Scott Berry: failure, the cost,
the numbers, but it was that sort

of leap when their, the, the trial
hadn't enrolled a patient yet.

I'll contrast this a little bit
with the Healy a LS platform trial

Craig Ritchie: Mm-hmm.

Scott Berry: where one of the beauties
of that very similar trial design,

they, the ice bucket challenge raised
money that they were able to fund the

first few drugs into the platform.

Form

Craig Ritchie: Exactly.

Yeah.

Scott Berry: and once they got
the first few in and they could

show, this is what happens.

We're getting great data, we're
enrolling patients, was lining up to

Craig Ritchie: Mm-hmm.

Scott Berry: a little
bit of that first arm

Craig Ritchie: Mm-hmm.

Scott Berry: thing.

And so this idea in in all platform
trials now, the same thing in EAD

happened in a Duchenne muscular

Craig Ritchie: Mm-hmm.

Scott Berry: They were
doing the same thing.

No company would be the first.

This idea of.

A loss leader or a repurposed
drug, something to show proof

of concept, I think is really
critical to these platform trials.

Craig Ritchie: Yeah.

And, and I think one of the, one of the
challenges we faced, and again, this is,

I mean, it might, it might sound like very
fine grain and very sort of, you know,

kind of, you know, governance, operational
if you like, but IMI projects are,

like I said at the beginning, they're,
they're, they're almost like a tender

where you have to pretty much commit to.

Right out the right out the gate
at the beginning of the project.

These are our work packages, these
are our deliverables, etc etc And

actually flexing the program in life is
really, really hard, if not impossible.

So if we wanted to repurpose some
of the dare say, if we wanted to

move some funding to actually have a
repurpose medicine, that was really not

really open to us as an opportunity.

So even though we kind of.

Thought, you know, this would be
probably a sensible thing to do.

There wasn't really the mechanism
within the trial or within the

program to be able to do that.

And, and I think the other thing, I
mean, it sounds, again very detailed,

but the, the way we were gonna sustain
the platform was to do the trials so the

money was gonna start flowing back into
the system because the sponsors would pay

for a trial and that would maintain the
cohort study, etc So without that trial,

then there was no sustainability because
the grant finished after five years and.

You know, again, I often, you know,
as, as you know, Scott, I've come into

the business world and, and you know,
you could almost argue there's a 64

million Euro investment, but at the end
of the five years it just disappears.

And actually think for all that seed
funding, or even, it's almost like a

little bit of a Series A, you think
they, they, they, there maybe could

and should have been a mechanism that
didn't rely just on the program for

sustainability, but actually said, you
know, we've made a big investment in this.

You know, let's, let's
throw some good money after.

Good.

But that, again, wasn't an option
for IMI or any other sponsor.

So we we were left where we were.

Scott Berry: I, I think it was
also a really interesting time in

the science of a platform trial.

Uh, in turn there, there
were several out there.

There was ipy two out there,
stamp P trials, several trials,

but it was a really oddity that.

That maybe a perceived risk for
pharma to go into this new odd thing?

Would regulators really trust data?

From then, COVID happened, and
really the only way to address

COVID was platform trials,

Craig Ritchie: Exactly.

Scott Berry: recovery trial, the REMAP CAP
trial, active operation, warp speed, the

science of platform trials in five years.

Uh,

Craig Ritchie: Mm-hmm.

Scott Berry: COVID to where we are
now, is it, it was incredible, uh,

acceleration of it that if we started
EPA now, I think it would've been

very different perception of it.

I think we'd go about it differently with
our lessons learned, but the industry

itself and its understanding of the
platform trial, I also think would've

been very different, uh, after COVID.

Craig Ritchie: Definitely.

It's slightly ironic, isn't it, that
COVID was probably one of the, was in

a sense the nail in the coffin for, for
epa, but it was the, the, the real proving

ground for, for, for platform trials.

So you, um, but I guess that's why we're,
like I said, we're dusting ourselves off

and we're trying to go again, you know?

Scott Berry: so, so dusting ourselves off.

Um, uh, uh, now after 2020,

Craig Ritchie: Yeah.

Scott Berry: you're the founder
of Scottish Brain Sciences.

Craig Ritchie: Yeah.

Scott Berry: is Scottish Brain Sciences?

Craig Ritchie: So I think, yeah, I mean,
so I set up this company about maybe

two or three years ago, and there was
a variety of different reasons for it.

I mean, but I think the most
important was that at a personal

level, um, you know, through my, so
I'm, so, I'm a clinical academic.

I'm a trained psychiatrist.

You know, graduated way back in 91,
worked at UCL Imperial Melbourne, various,

uh, you know, academic institutions.

And I was fortunate enough to be involved
in some, like, like with EPA and other

and other programs, cutting edge science
and really learning so much about

what was possible, um, in terms of our
understanding of neurogenic diseases.

Early detection.

You know, we've got
blood-based biomarkers now.

We've got, you know, incredible imaging
technologies, all these wonderful things

happening, new therapies being developed.

But that world was a million
miles away from my clinic.

So when I actually went to clinic on a
Tuesday afternoon in Edinburgh, um, it was

almost like the clinic that I helped to
set up in 1997 in Melbourne, Australia,

you know, so although the science had
been advancing at an incredible rate.

Clinical services, were actually getting
further away from the science and

there's very few branches of medicine
where that gap is actually widening.

I know there's always gonna be delays
between science and implementation,

but I was really sensing that we were
actually getting worse rather than better.

Maybe in COVID played a part in that.

We all had the experiences of what
happened to people with dementia

during the, during the pandemic.

So I, I thought, you know, I was.

What am I now?

So I was 54 years old, 53, 54 years
old, and I said, you know, almost

like a final roll of the dice.

Rather than trying to continue to
do this through the academic and the

pub public sort of sector, I thought
I'll, I'll start up a company to try

and bridge that translational gap.

And that's what Scottish
Brain sciences is.

So for people inside who knew what
EPAD is, I've, I've actually tried

to commercialize EPAD um, but
doing it through my own company.

So you're not relying on
multiple other stakeholders.

actually saying, you know, let's, let's
bring all this in-house to try and develop

the, um, the, the, the, the, the assets
in some ways that we had with an epa, but

doing it through a commercial vehicle.

Scott Berry: Yeah.

So now you're setting up,
um, you're setting up.

Sites, uh, across Scotland, across Europe.

Uh, I think you're physically right
now as we look at you, you're in the us

Craig Ritchie: Yeah.

When asked.

Scott Berry: you're setting up
almost this readiness cohort.

Craig Ritchie: Well,
we've, we've set it up.

So we, we have a cohort called Iona.

Um, Iona is IONA, but it's, um, it's a
Scottish island, a beautiful Scottish

island off the west coast of Scotland.

That's the, that's, that
is the readiness cohort.

Um, and maybe have shared the protocol
with you, Scott, if I haven't you, when

you look at it, you'll say, that looks
vaguely familiar because it's, it's,

it does look a little bit like epa, uh,
for, for a variety of different reasons.

Um, and that's the, that's the cornerstone
or the foundation of, of everything

we're doing in the company is, is
that Iona Longitudal cohort study.

And it has all the same,
you know, potential outcomes

that we've talked about.

Um, you know, using the data, using the
biobank for discovery, but also using the,

the cohort study for as a readiness cohort
for, for, for, for putting people into

trials and our experience in Scotland.

And where we've been running this for
maybe a year and a half is it works,

it really does work in terms of, you
know, engaging people and getting people

into trials at unprecedented levels
that, that we've seen historically.

Scott Berry: Does that, I jumping back to
this idea that you felt like the clinical

side was 1997 and it was divorced a
little bit, you think that bringing this

and bringing these cohorts and patients
and readiness is, is helping part of

that problem in addition to this, that

Craig Ritchie: Yeah, definitely.

Scott Berry: patience.

Craig Ritchie: I think, I think one
of the things also that we, we learned

from epa, um, was, I've mentioned
work package eight, which was the

ethics, legal and social implications.

You also remember we had work package
six, which was communication and

engagement, and um, that again for
people working inside the space.

Recognizing that you needed
to invert has changed.

The narrative was really important.

Getting people to understand that, and
those are the people can be the public,

but can also be fellow clinicians.

That this is a midlife disease
that expresses satellite

as a dementia syndrome.

You, you needed to keep banging that drum.

You need to keep getting that message
out there through various channels.

So the readiness cohort in, in,
in, in Scottish brain sciences.

Um.

Is the kind of, again, the foundation, the
empirical basis for, um, Anna Borthwick

who was in charge of work package six and
EA now works for Scottish Brain Sciences.

So that part of the company is absolutely
crucial, um, to use that patient voice or

the participant voice to channel that, to
do engagement work, to make people realize

that there is real hope and expectation
that we can, you know, we can, you

know, eventually cure these conditions.

So I think as well as the data.

There's also, like I say, well the
numbers, there's also the narrative and

I think that's something we're, we're
committed to also, um, developing.

Scott Berry: So are, are, are
participants in, in your, your readiness

cohort in Scottish brain sciences.

You're using these for
pharmaceutical clinical trials

Craig Ritchie: Yeah, absolutely.

Scott Berry: access point.

Okay.

Uh.

Craig Ritchie: And I think one of the
things that, you know, it was really quite

gratifying in many ways was that when we.

I remember at the beginning I said that
the, you know, the readiness was based

on two things that yes, it was the data
and the, and, and, and the, and the

characteristics, but it was also the
readiness of the individual person.

And I remember it's quite sort
of poignant moment, Scott, but

I remember the first participant
from the, from the Iona cohort.

I actually took consent
to come into a trial.

Um, and it was completely
different from any other consent

I'd previously done because.

She'd been part of the cohort study.

She'd been off to the unit.

She knew my research staff, they knew her.

There was this engagement.

She was, she would, I mean, virtually,
it was like, where do I sign?

Scott Berry: yeah,

Craig Ritchie: Thank you.

You know, thank you for, you know,
for, for offering me this opportunity.

And I just, it just made me realize that
EPA would've worked from that level.

You know, the, the, the engagement
we had from participants, research

participants, had we gone back to
them with the platform trial, I think

there'd have been a, a gratitude.

Um, then we were, we were
putting in place a trial.

So, you know, it was a bit of a
bittersweet moment, to be honest.

Um, but

Scott Berry: Yeah.

Craig Ritchie: yeah.

Scott Berry: Yeah.

Yep.

Yep.

Now, uh, an another interesting part
of this is we were, when, when EAD

started, we were probably in the midst
of, I don't remember exactly the number,

but plus failed phase three trials.

Uh, nothing worked in Alzheimer's disease.

Lots of reasons for it.

Drugs, understanding the patient.

Do they actually have Alzheimer's?

Lots of.

Things, the, the stage
of disease and all that.

Now we're at a point where
we've had some successful

Craig Ritchie: Yeah.

Scott Berry: modifying treatments.

We've have regulatory approval of them.

Must be gratifying from that
perspective, uh, in terms of treatments.

But now, where do we sit today in terms
of drug development altering this disease?

Are you optimistic of,
of where we sit today?

Craig Ritchie: Well, I'm, I'm,
I'm, I'm, I'm eternally optimistic.

I think, you know, we, we, we,
we understand this disease.

We're beating it, we we're
getting to understand lots of

disease pathways and mechanisms.

Um, from, from the laboratory
work and from the, from the data.

It's translating that into therapeutic
interventions as a critical thing.

And I still think we have a
problem because the clinical

trials ecosystem, if you like, in
the Alzheimer's space is still.

20th century.

So these trials still cost
a fortune to actually run.

So the, the, the, the bar to actually
embarking upon a phase three clinical

trial is, is incredibly high.

And I think one of the things that we
haven't really talked about is, but

we, we kind of ran the numbers, um,
on EPA and thought that, that the cost

of delivering a trial to the sponsor
would be quite significantly lower.

Than it would've been had they
just done it on their own.

Um, so I think, again, you know,
the science isn't the problem.

I've, I've, I've been
seeing that for years.

I think the problem is actually
operational and, and, and, and

sort of more sort of a, you
know, um, practical aspects.

Um, but, and that hasn't changed.

And I still think there's, there's,
there's still a little bit of a

copy and paste in trial design
today, uh, from, from trials we

used to do in the 20th century.

Well.

Like you've mentioned, other areas like
MS and MND and cancer has, has moved on.

Um, but we we're still a bit stuck.

Scott Berry: Yeah.

Yeah.

The um, uh, so, um, so within
that Alzheimer's space, part of

it is, will a platform trial,
you mentioned the, the huge cost.

So if, if somebody wants to go in and run
a trial, phase two, phase three, this huge

cost, the platform trial could create.

Cheaper shots on goal, more shots on

Craig Ritchie: Yeah, more so.

Scott Berry: the, the
ecosystem as you described.

I also think that Alzheimer's is probably
given the enormous burden that Alzheimer's

places on, on healthcare systems that
a platform trial at the payer level, at

the healthcare system to understand who,

Craig Ritchie: Mm-hmm.

Scott Berry: for these treatments,
uh, are, are right, is, is.

Saves huge amount of money, uh, for that,
that that's also a potential, a little bit

different than drug development, but one
at a understanding the various drugs that

come out and are, are, are approved to
some level, could be enormously impactful.

Craig Ritchie: Well, I, and I think
one of the, one of the things that we,

we saw in EPA was of course, research
centers who are running the, the trials,

whether it's in Amsterdam or in, or in.

On in Stockholm or in Indeed in
Edinburgh, gonna be less than Edinburgh

than other parts, to be honest.

But they were also clinics.

So there was this kinda adjacency between
clinical research and clinical practice.

So I think to the point you're making
that, you know, when you're running

clinical research, it, it, it's a shorter
gap if the trial works, if the, if the

drug becomes available, you are the
investigator who becomes the doctor.

Your research staff become the
nurses and the doctors that.

You know, give infusions
and monitor for safety.

So, so I think this ecosystem that,
that, that, that we develop from a

research setting leads to also be the
ecosystem where, where people get treated.

So you, the, the trial participant becomes
the patient hopefully quite seamlessly.

And again, that's something within
Scottish brain sciences we're

trying to do, we're trying to
deliberately blur the between clinical

research and clinical practice.

The pair, of course, like you say.

You know, should be biting your hand off
because what you're actually doing is

you're much better at patient selection.

You're much better at, you know, ensuring
that you have the data to hand that

says, is the drug working or not working?

So in like in a trial,
we wanted to fail fast.

You know, we wanted to kill arms.

We wanted to, to look at things that were
working and, and, and promote them and

look at other things that weren't working.

And, and, and, and maybe, like I
say, make that go no go decision.

The evolutionary analysis as we
called it, and I think that's

true in clinical practice.

You know, is this drug
working for my patient?

If not, let's try something else.

But I think at the moment in clinical
practice in the Alzheimer's space,

it's kind of a one size fits all.

And we don't have that, that kind of, you
know, approach that, as I keep saying,

other branch to medicine do, like an
oncology or HIV medicine, we don't have

that repertoire or that, um, or that,
um, portfolio of medicines and tests

to really understand what's going on.

So.

Scott Berry: So you, you, you talked a
lot about the benefit of the translation

from the research to the patient.

other part that just seems so looking
at the outside in is we learn about

what works from less than 1% of.

Patients with a syndrome, with a disease,
the more that we could tie together

infuse clinical practice and research.

And we learn from patients
that are treated e every day.

I mean, there's an explosion in learning.

If we could learn from people taking
treatments, uh, outside of research,

what we call traditional research.

Craig Ritchie: Yeah, and I think, I
think there's, there's, we're talking

earlier about the, the therapies that
have actually made it through the FDA and

the EMA and the MHRA, you know, namely
Umab and Lecan, and there's attempts.

Dare I say it, to put in place
phase four trials to put a

post-marketing kind of data collection.

Um, and if I can be candid, I don't
think those things should have probably

been designed three years before
launch because I think we're not really

making that seamless transition to, you
know, from phase three to phase four.

I mean, I think everybody knew that when
these drugs with the side effects and the

issues and the challenges that we face
in using them because it's so difficult.

Different from what we used before.

It should have been a same, a seamless
phase three, phase four program that

people were up at, but we, we've
probably lost two or three years

in terms of setting up phase four.

Now, again, I'm not saying that SBS
is a solution to everything, but

you know, if, if we do have people
who either go into a trial or go

into a, onto a, onto a treatment,
they stay in the IU in a cohort.

So we continue to collect
that data, whether they're

on a trial or in a treatment.

And, you know, as long as the, you
know, company survives, we should

be able to develop that longitudinal
data set, follow the person on their

entire journey, plus or minus drug,
plus or minus, you know, trial.

Um, and that data will be
obviously incredibly important.

And then there's the real world data
for people, you know, that needs to

be collected as well outside of that.

But I, I still think that a lot of that
real world data that we have in memory

clinics around the world is, isn't.

Necessarily collecting the data that
we really need to understand the issue.

It's a little bit, um, lacking in
veracity, uh, for what we actually need.

Scott Berry: Well, this is awesome.

It sounds like, uh,
incredible stuff going on.

You're, you're, you're jetting
around the world setting this up.

Craig Ritchie: Yeah.

Scott Berry: back in epa, uh, with maybe
a late night discussion in a drink.

Craig Ritchie: Yeah.

Scott Berry: you, um, uh, pushed on
me the, the, the importance of sleep.

Craig Ritchie: Yeah,

Scott Berry: uh, for
Alzheimer's, for, for health.

Are you sleeping well, Craig?

Craig Ritchie: I'm sleeping a lot better.

Thank you.

I think, um, yeah, you gotta
gotta practice what you preach.

And, and I think that's a really important
point, by the way, I mean, I, I know

we're coming to a close, but we've talked
about drugs, we've talked about, you know,

biology, but there are so many things.

At a lifestyle level, at managing
sleep, managing diet, managing exercise,

these types of things, which will
probably give you the best shot of maybe

never getting Alzheimer's pathology.

And if you do, you know, you
mitigate some of those risks.

So, you know, let's not, let's
not just focus on the drugs.

I mean, me have, give a pal to, as you
know, our good friend is, is, is, is

leading in that with the finger study.

So I think, you know, wrapping
around the, the non-pharmacological

lifestyle with the pharmacological
is, is ultimately the best solution.

And yes, I'm sleeping a bit better.

Thank you.

Are you

Scott Berry: I, I actually am.

Yes.

Craig Ritchie: good?

It's good to hear.

Scott Berry: it a priority.

I, I've

Craig Ritchie: Absolutely.

Absolutely.

Scott Berry: I, I also remember
as, uh, what was on your,

your, your, your music device.

I don't know if it was an iPod.

I don't remember at the time, but you
were an Eric Church Springsteen fan

Craig Ritchie: am still am.

Yeah.

Yeah.

Scott Berry: I, I, well, I, I remember
one of the, the, the best sort of lines

from that, which probably appeals to
somebody in, in a psychiatrist and, and is

funny how a melody sounds like a memory,

Craig Ritchie: It's beautiful, isn't it?

Yeah, yeah, yeah.

Scott Berry: which,
which seems very apropos,

Craig Ritchie: I think,
I think you, yeah, bro.

Yeah.

Good, good place to finish.

I, I'm gonna start, I'm gonna put
that onto my, uh, Spotify now.

Just, I'll re, I'll
revisit that Eric Church.

Yeah.

Scott Berry: I, I, I thank
you immensely for joining.

Craig Ritchie: Thanks Scott.

Scott Berry: was fun.

Appreciate it.

Craig Ritchie: Pleasure.

Absolute pleasure.

Thanks Scott.