Platform Trial in Psychiatry with Dr. Husseini Manji

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, uh, in
the Interim Very Consultants podcast

of all things science in clinical
trials, statistics in clinical

trials, innovation in clinical trials.

Uh, have a really cool topic today.

Uh, I will introduce the topic,
but first I have really two

very special guests, uh, Dr.

Mike Crams, a neurologist and senior
medical scientist at Barry Consultants.

Mike is a, uh, 30 year veteran of
drug development, uh, in neurology,

and even, uh, has been at Pfizer, YFJ
and J and headed up, uh, quantitative

sciences at j and j, uh, before
joining Berry Consultants this year.

So, welcome Mike.

And, uh, interestingly for the topic
today, Mike was really a driving

force behind the creation of EPA
D and IMI funded platform trial

in Alzheimer's, uh, uh, for that.

And I'm also joined today by Dr.

Husseini Manji.

Uh, and we could spend our whole
day, uh, with, with the, uh,

accolades for, for, uh, Husseini.

He is currently.

Uh, at Oxford University, he's co-chairing
the UK Government Mental Health Mission.

Uh, he is a professor
at Oxford University.

He is the past global therapeutic head
at for neuroscience at j and j where

he and Mike, uh, worked together there.

Uh, he, so really interesting.

So currently in academia.

Uh, government work.

He was at the NIH where he headed
up the NIH Mood and Anxiety

Disorders Program, the largest
program of its kind in the world.

Also the laboratory for molecular
pathophysiology at the NIH.

Uh, he's a, he's inducted into
the National Academy of Medicine,

has multiple prizes, but I thought
this one was sort of interesting.

He was one of the 14
inaugural health heroes.

By Oprah Magazine.

So welcome, uh, Husseini.

Husseini Manji: Um, thank you.

It's a pleasure to be here with
you today and participate in

this very timely discussion.

Scott Berry: So what we thought
we'd do today, we, a a, a few

episodes ago we talked, uh, about
the Heal a LS platform trial.

That's a trial that's running
eight arms already in there.

It's sort of full speed,
uh, uh, running in that.

Uh, we thought we'd talk about the
early stages of a potential platform

where I, I think Husseini, one of the
things you're really interested now is,

is precision medicine and psychiatry.

Um, now I know you, you were.

Involved with j and j and his ketamine,
uh, one of the fir the first, uh,

antidepressant in, in 30 years.

Uh, so you've been down this road.

So tell me your interest in precision
medicine and psychiatry and what this

platform trial could potentially,
uh, you know, uh, solve and be.

Husseini Manji: Great.

I, I think this is a very
timely and exciting discussion.

I'll just take a step back.

Um, you know, you probably have a
very broad and diverse audience.

Some of whom may be less familiar with
the impact of serious mental illness.

So I'll just take a moment about,
you know, the magnitude of the burden

with serious mental illness, and then
go into why I am so excited about

precision medicine in psychiatry.

So I think mental illnesses really
represent a significant global

challenge with profound health,
economic, and societal impact.

One of the reasons they're so
devastating is that by and large, they

strike individuals relatively early
in life, usually late adolescents or

early adulthood, and they're lifelong.

So they're the chronic
diseases of the young.

And not only do they cause direct pain and
suffering, but they affect every aspect of

people's lives, including physical health,
social functioning, economic, economic

functioning, and um, academic performance.

So there's a real need to come
up with improved treatments for

these conditions because you know
the unmet need is staggering.

And yet despite this unmet
need over the last few years.

Many large pharma companies
have actually exited this space.

And it's a, you know, so one could
say it's actually a reasonable

business decision on their part.

And why I say that is that they've
been concerned that compared to many

other, medical illnesses, these are
very complex and, it's not been as

easy to come up with this precise
target for a variety of reasons.

One is that the brain really is
the most complex organ we have,

and it's relatively inaccessible.

Compared to peripheral organs.

So we do a lot with imaging, we do
a lot with peripheral biomarkers,

but you can't directly do a brain
biopsy, so you've gotta be, you

know, a little bit more indirect.

Secondly, as you may well, um,
know that the animal models don't

translate very well into humans.

And so we've got sort of get into humans
early on, and that could be one of

the real advantages of this platform.

The other thing to mention is that
while they're amongst the most heritable

of a lot of medical conditions, they
arise at the inheritance of hundreds

of suscept susceptibility genes that
interact with environmental factors.

So there's no single driver mutation
like there is an oncology I.

And then probably the most relevant
for this discussion is that the Neology

is based largely on a syndrome of
subjectively determined criteria.

So you basically ask people to
tell you about their mood, their

appetite, their energy, and so on.

And there's almost no doubt that we
put these labels like depression,

bipolar, schizophrenia, on a
group of heterogeneous disorders.

And not surprisingly that if you take,
heterogeneous groups of disorders and

basically apply a broad label to them
and take a one size fits all approach

to them, things don't work as well.

And so that's why we're so excited
about the idea of precision psychiatry.

I.

Can we really get to this away from
this one size fits all approach

and similar to what's happened in
areas like oncology in particular?

Can we start to move into more of
a precision based approach where we

can use patient specific information?

To basically divide the broader clinical
population into subgroups that are more

likely to respond to specific treatments.

So rather than focusing on symptoms,
behaviors, neurotransmitters, et,

cetera, we can start to look at illnesses
based on their fundamental biology.

Neuronal circuits other biology and
use that as a way to really get into

some subgroups who may preferentially
respond to different treatments.

And that's where I think a lot of the
advantages of what you and Mike are

driving in terms of precision medicine,
biomarker based adaptive trials

could be game changing in this space.

Scott Berry: Uh, uh, okay.

So, uh, touched on a
lot of things on this.

So, the, a number of platform
trials have, have come out of,

uh, patient organizations where
they've recognized disease, uh,

particular diseases are really hard
to, to, to find successful things.

It's hard drug development, it's
expensive, low likelihood of

success, but the need is there.

Husseini Manji: Yeah.

Scott Berry: so this feels
like a very similar situation.

So there's still great need.

uh, development is hard.

Uh, success is unlikely, uh, small.

Um, uh, there are huge
challenges and so a.

Platform could potentially create,
uh, uh, easier, uh, ways in for drug

development, uh, potentially increase
rates of success, lower the burden

for shots on goal kind of thing.

That sounds like a a, a huge part of this.

So let's think about what this are.

Are you thinking this is, this is not.

Comparative effectiveness, so we're
not looking at things already approved.

Uh, healthcare, how they treat them.

You're thinking about phase two
type exploration is where multiple

pharmaceutical drugs may come into
this, that that's kind of a sweet spot.

Husseini Manji: To, um, I think
you hit the nail on the head, so

I strongly believe that's where
the sweet spot is going to be.

So there's actually been a lot of advances
in neuroscience over the last 10 or 15

years, and so there are some novel and
unprecedented targets to be interrogated.

But as you alluded to, in, in all
fields of medicine about 90% of these

things are failed, are going to fail
despite the best, science, et cetera.

So if you could have a platform
trial where you could interrogate

a number of these novel, pathways
mechanisms in these phase two type

of clinical trials, et cetera.

Even, failures as failing
early is also very important.

So you can redeploy resources to
things that might be more successful.

And as I said earlier, there's also a lot
of reason to believe that while we've got.

Made a lot of advances in the science.

These really are very
heterogeneous groups of disorders.

So even if you had, quote
unquote the right target, if you

apply it to all comers, you're
probably gonna lose a signal.

Whereas if you could apply it to
a targeted population, then you'll

really know whether it works or not.

And again, based on the work you and
others have done with biomarkers, would

allow us to, move in this direction.

I'll just mention one more
thing, related to your comment.

So I think in my opinion, it's
absolutely correct that the sweet

spot may well be the, Phase two proof
of concept trial types of trials.

But there is reason to believe, so there's
a lot of, scientific data to suggest

just like in neurodegenerative disorders.

In neuropsychiatric disorders,
the immune system, I.

Actually seems to play a major role.

Once again, it's not going to
be in all comers, but if you can

identify people based on some
sort of immune diathesis, they may

respond to an immune targeted drug.

And the reason I'm bringing this up
here is that, there are a number of

these drugs that have been developed
for, example, autoimmune disease like

rheumatoid arthritis, inflammatory
bowel disease, psoriasis, et cetera.

That may hit the right targets
in terms of say, IL six, TNF,

alpha IL 1223, et cetera.

So what we're thinking is that there
may also be the possibility of using

this for, approved drugs, but in a
sort of repurposing, approach where we

can see, with the immune, neuro immune
being one of the best examples, I think.

Okay.

Scott Berry: Yeah.

Uh, so, uh, in, in thinking about the
precision aspect of this in oncology,

for example, um, we, we have, there's
the place the tumor exists, head and

Husseini Manji: Yeah.

Scott Berry: breast cancer, lung cancer.

Yet there are drugs that
go after targets, uh,

Husseini Manji: Right.

Scott Berry: may work across a
span of these because it targets a

particular, uh, uh, aspect of, of
tumors regardless of where they are.

you think that this might be similar,
that it's not so much bipolar, uh, it's

not so much schizophrenia or depression,
but it's somebody who is receptive?

To IL six, that, that, so the platform
might enroll a quite wide range of,

of typical indications, if you will,

Husseini Manji: Yeah,

Scott Berry: yet a single drug, IL
six receptor antagonist or IL 23 or

something, or, uh, autoimmune might
hit across a span of these, but

only a subset of them that have the
indication is that the, the notion here.

Husseini Manji: that's
absolutely the notion.

So again, if you look at sort of our
current diagnostic classification

for these disorders, and there's
something called the DSM.

Um, it's basically a checklist
of signs and symptoms.

For example, if you look at depression,
major depressive disorder, depressed

mood, and hedonia, the inability to
experience pleasure, lack of motivation,

lack of drive, sleep, appetite, energy.

And yet many of these symptoms actually
cut across many of our, um, illnesses.

So they're present in bipolar
disorder, schizophrenia, et cetera.

And what we've been trying to do as a
field is exactly what you said is try

and map some of these symptom domains.

Onto biology or pathology so that the
idea might be an IL six monoclonal

antibody, or IL 23, et cetera, could
target the circuits, neuronal circuits

responsible for these symptoms.

Whether we call you depression, bipolar.

Schizophrenia and so on.

And so there's something that's
been, um, the term that has

been used is trans diagnostic.

And the very good news is that regulators,
um, both the FDA and in the uk, we've

been interacting with the M-H-R-A-I.

Um, sort of get it.

They understand that, you know, sort of
our old classification system probably

isn't as conducive to coming up with novel
treatments, so they're very willing to

look at this trans diagnostic approach.

Clearly, regulators need
to see the evidence.

You know, they can't
just take a word for it.

But, so for example, there's a lot of
interest in the possibility that if

you could show that something works,
for example, for this domain called

anhedonia, which is very impairing,
you could potentially, potentially

get the approval to use it to treat
anhedonia, whether your official

diagnosis is major depressive disorder,
bipolar, schizophrenia, and so on.

So what you said is spot on.

That's the way we're thinking about this.

Scott Berry: Yep.

Uh, alright, Mike, I'm gonna go
farther into design, but I feel

like I, uh, I, I have their stuff
I've left out before I jump into

more of what this could look like.

Mike Krams: I think, uh, you have, uh,
asked all the pertinent questions and,

uh, Sini, it's a pleasure listening to you

Scott Berry: Yeah.

Mike Krams: and it's an even greater
pleasure anticipating what type

of, uh, future work that will be.

So, uh, Scott, keep going.

And Sini, keep going.

Yep.

Yep.

Scott Berry: I'm gonna come
back to you, Mike, and ask about

thinking about, and I know, uh, Dr.

Manje can, can answer this question,
but pharmaceutical companies and

their perception of such a thing.

Husseini Manji: Yeah.

Scott Berry: you know, the, the, the
important stakeholders in all of these

seem to be regulators, pharmaceutical
companies, sites, and patients,

Husseini Manji: Yeah.

Scott Berry: perception of all of this.

And if one of those breaks down,

Husseini Manji: Yeah.

Scott Berry: tend not to work.

Uh, even one, so.

Um, it, we, we, in I SPY two, it
was neoadjuvant breast cancer.

already, uh, uh, broke, uh, the cancers
up into hormone receptor status.

And HER two status was sort of recognized
that these are different diseases and

it was, uh, uh, also mammoprint status.

But, uh, so drugs would come in
and the trial already looked for

differential efficacy by those.

We have, uh, GBM Agile, uh, is a trial
looking at glioblastoma, where in that

case are some, uh, strata that are
broken up, but there a drug can come in

and say, I'm interested in mutation X.

Husseini Manji: Mm-hmm.

Scott Berry: Another drug might
not care about mutation x.

We have other trials that are trying
to do precision medicine, where largely

they come in and they treat everybody,

Husseini Manji: Yeah.

Scott Berry: then it's kind of data
analysis after the fact looking

for heterogeneous treatment effect.

What do you think?

A pharmaceutical company, are the
drugs that are out there, are they

going to be, uh, is this, the science
has differentiated these diseases?

It doesn't sound like that's the
case, that there's a whole bunch

of different potential drivers
it may be the drug defines.

The heterogeneity in this
case, or are we largely looking

for it by treating everybody?

What do you think the, the, the, the
drugs out there are going to be and what,

what should the trial try to answer?

Husseini Manji: Yeah, so I, I
think both things are very germane

and there are efforts which are
looking at, you know, sort of.

Treating people with, you
know, a variety of drugs.

So for example, when I was at the
NIH, we did a trial of 4,000 depressed

patients where they were sequentially
treated with different, um, modalities.

If they didn't respond, they
went on to this and so on.

And, um, a lot of, um, byop biological
information was collected, various

kinds of omi et cetera, to say, can
we sort of see, you know, what the.

Determines response to this
modality of treatment, et cetera.

But I think the former aspect
you mentioned is actually

going to be more exciting.

You know, prospectively saying, look.

We have a drug that affects this neuro
immune cascade or this hippocampal

plasticity cascade, or you know,
this sort of, um, excitatory I

inhibitory balance, et cetera.

We think it should work on
this sort of subtype of people.

Can we recruit those types of
subtypes of patients and in fact,

demonstrate that this holds up as you
know, you know, sort of companies.

Um, so one of the things about
pharmaceutical companies is that

I would say, you know, probably 15
years ago or so, people wanted to

treat all comers because you had
a larger, you know, population.

I think now there's a recognition that
if you can treat a subgroup really

well, and maybe your drug becomes the
treatment of choice for that subgroup.

That's actually pretty good.

So pharmaceutical companies have
gotten away from this notion

of, let's treat every depressed
patient and hope for the best.

So they're much more interested in
subgroups and so I think they would be

more interested, you know, in this sort
of notion that, okay, if we think these

sort of immune mediators as an example.

Might work.

Can we identify those people?

And you know, I think we should come back
in a moment to, you know, what biomarkers

are, um, ready for prime time, if you
will, in psychiatry with those sort of

biomarkers and see if it holds up so that
we can sort of say, yes, our um, drug.

It's preferentially going to res,
you know, treat these patients.

As you know, one of the challenges
in medication development is

also, um, getting payers to pay
for medication because there's

so many generic medications.

So if you could show with data, I.

That using this biomarker, it really
increased the probability of success

that this population will respond.

There's the possibility that the payers
would be willing to say, okay, we'll

give you a higher price because you're
not going after all comers, you're

going after this targeted subgroup.

So that's, I think, where more of the
action is going to be because, um, a

lot of what we are interested in, um,
my group is in the earlier phase study.

I think pharmaceutical companies
would be very receptive to sort of

putting a bunch of drugs from different
companies into the same platform.

You know, when it's a late stage phase
three asset, et cetera, they may be a

little bit less, um, willing to do that.

But in the early phase where this would
hopefully be, um, generating proof

of concept and if it works, you can
go and do your own phase three study.

You know, maybe it might be under
the auspices of this initiative,

but I think they'd be willing
to do that because of the, um.

Uh, markedly enhanced rigor, efficiency,
speed that the platform trial

would, you know, bring to the table.

Scott Berry: Hmm.

So there, so, so a skeleton
of what this could look like.

So you have a number of sites,

Husseini Manji: Yeah,

Scott Berry: and it's

Husseini Manji: I

Scott Berry: the, there's
a master protocol.

That defines some large level of,
of, uh, inclusion exclusion criteria.

Husseini Manji: right.

Scott Berry: You, you have the ability
with a standard battery of biomarkers

that, that you're probably looking
always the ability to add a biomarker,

Husseini Manji: Right,

Scott Berry: needed in that.

But

Husseini Manji: right,

Scott Berry: standard set of biomarkers.

Um, a, a drug you, you'd be
looking at a wide range of.

Potential treatments,
a drug would come in.

We're thinking about this in phase two.

drugs could come in and they're actually
interested in treating everybody.

Husseini Manji: right.

Scott Berry: it could potentially be,
or they're interested in treating a

subset by traditional indications,

Husseini Manji: Yeah.

Yeah.

Scott Berry: but then
a drug could come in.

Pharmaceutical company wants to
treat those that have high or low

biomarkers of a particular type.

Um, and they said we would like to
have our drug tested in that subgroup.

they might be further looking for,
uh, heterogeneous effects within

that subgroup, uh, of those.

But, and so one drug comes in and
it's, it's enrolling, uh, uh, in all.

types other drugs come in and they're
specific, and, and the, the potential

patients in the trial are having a,
a, a set of biomarkers done, which

would inclu their, their ability to,
uh, be included with any of the drugs.

They're then randomized it, uh, to these
drugs or a, or a placebo, uh, within

that, for those, they're eligible for.

We could largely have similar visit
schedules and things collected on these

patients within this master protocol.

What, what kind of things seem
to work or don't work with that?

Husseini Manji: So I, I think
you've really, um, captured things

really well, and hopefully we can
include you and Mike as consultants

when we're designing things.

I'll just take a few of the, you know,
very salient points you mentioned.

So one of the things in the UK as part of
this, um, mental health, it's now called

Gold's Program, used to be called Mission.

We've set up this network of 15 clinical
research sites throughout the UK to

do basically exactly what you said.

Um, you know, sort of have this network
so you can, you know, both have large

numbers of patients, everyone, you
know, following the same procedure

for the patient evaluation, for the
biomarker collection, et cetera.

But I think what's also very important
is that we also have this in the uk.

Um, some of the sites we have are at
what you might call the heavyweight

sites, the Oxford, the Cambridge,
the Kings, the UCL, et cetera.

Many of these sites are in areas
where you have larger populations of

individuals from different socioeconomic
background, from different, um,

racial, ethnic backgrounds, et cetera.

So you are basically also trying to
get the information, you know, if

this thing works, does it actually
work in general, or what population

does it work in, et cetera.

As part of that, in initiative,
we have a major OMI initiative

where we're collecting saliva
and plasma in particular.

Um, one of the challenges we have,
as I mentioned earlier, is that while

there's strong reasons to believe
heritability plays a big role,

these are genes of small effects.

So you don't have the driver
mutation, so you need to think

more also about transcriptomics
and metabolomics, et cetera.

And as you know, whenever you're talking
about measures that are more sensitive

to change compared to sequence variants,
um, they're more, um, subject to noise.

So you really have to
standardize things, et cetera.

One of the things in what we are trying
to do is part of this thing called the

Mental Health Goals Program is really
emphasize that the biomarkers need

to work in the trial, but they need
to work in the real world as well.

And that's where we have one of the
additional challenges in psychiatry

is that we've done, I think, some
phenomenal work with very sophisticated

brain imaging, for example.

F, um, fm, FMRI with specific task
or magnetoencephalography, et cetera.

And you could do it in academic
sites for the trials, but in the

real world, someone in rural Alabama
or in Nottingham, et cetera, it's

not gonna go for those things.

So they're, these biomarkers have
to be related to things that could

be routine, inexpensive, accessible.

So we're putting a lot of effort in
terms of, even when we're trying to

look at the brain imaging signature.

Try and relate it to a peripheral
signature, which could be plasma,

for example, saliva or a digital
signature, so that these things can

be utilized, be utilized widely.

The other thing we're doing that
other companies are doing as well, I.

Is for example, say you think
someone might have a problem

with hippocampal plasticity.

There are some cognitive tests and
for example, Mike would be very

familiar with them that you could
do on a computerized battery and in

your home, and that would tell you
that you have this hippocampal in.

Plasticity impairment or with EEG, you
can send these caps to people's homes who

have these EEG leads connected to them
and you, you're using machine learning

and artificial intelligence to gather the
information from a single lead electrode.

You know, it's not gonna be as precise
as a 64 lead, you know, um, EEG

laboratory test, but it's good enough.

So I think coming back to what you said,
um, everything you said is spot on.

I'll come back to placebo as well.

So that's one of the other sort
of challenges in psychiatry is

that patients with things like
depression or anxiety disorders.

We strongly believe that when you enroll
someone in a study and you give them

hope and you give them, you know, first
time in their life this thing has been

explained to them and they're being
supported regularly, et cetera, I.

There tends to be a somewhat high placebo
response, but I think, I think placebo

is driven by biology and in the field
of pain that's been sort of born out.

So, um, people respond to placebo in pain
trials as well, and some studies have

demonstrated that if you pretreat someone
with an opioid antagonist, you block the.

Placebo response to pain suggesting
that you're basically actually

releasing your endorphins, which
are giving you the placebo response.

So I think it's not farfetched
to think about the possibility

that through this platform trial
there will be placebo responders.

Can we even identify the signature
that predicts a placebo responder?

Because that would help
companies a lot as well.

Okay.

Scott Berry: Yeah.

So, uh, so awesome.

So Mike, I'm gonna turn to you with.

Who could sponsor this?

How do we, uh, you, you know what?

Knocking down barriers, where do we go?

Uh, and, and something I want to touch
on that, I think a, you, you talked

about these biomarkers, the exploration,
there's a lot of disease learnings.

If you had multiple agents that came
in here and you're doing these various

biomarker analyses, you're looking
for heterogeneous treatment effects.

As more and more drugs come in,
you have a huge resource to learn

about the diseases themselves

Husseini Manji: Yeah.

Scott Berry: a, uh, as a, uh,
to move the disease forward.

Meanwhile, you're also
testing these drugs.

You're, you're creating a lower
barrier for pharma to come in.

They can take more shots on goals.

They, you know, this, this, this,
uh, raises everybody in this.

So, Mike, I know you, you, you
went to the IMI, we created epa.

we'll talk about some levels of success
in, in aspects of this, you know,

where, where do you go if this, this
idea, this ideation is sort of there,

is this an academic funded thing?

Is this a government funded thing?

Should this be a nonprofit, should
be a profit funded thing, pharma?

Where do we go?

Mike Krams: So the right answer to this I
think has come out of all the experience

that we already have with platform trials.

I don't think the answer
is, this should be.

Organized out of an individual pharma
r and d sponsor because there will

be, um, uh, competing interests
from one sponsor to the next.

So that's not a good model.

I think what's, uh, quite successful is
the setup that we have, for instance, in

GBM Agile, where dedicated group outside.

Of a pharma, uh, r and d company,
also not a academic group, but a very

skilled group of, uh, integrators.

I think that could work very well.

But can I just add, uh, sort of the
historical journey, uh, to this?

Scott Berry: Yeah.

Mike Krams: You ask who should we go to?

I think we should go to patients
because patients would have.

More than anybody else in interest and
a sense of urgency that there should be

great advances in a reasonable time as
opposed uh, to the inefficiencies that

have been self-inflicted by unnecessary.

Competitive perspective.

So the patient perspective is clear from
a, um, neuroscientist, uh, scientist

perspective and clinician's perspective.

Equally, everybody would want
more efficient knowledge creation.

And so the question is how can we also,
uh, encourage and convince, uh, sponsors,

uh, within the pharma r and d world?

And so, uh, you know, uh, how much.

Innovation is encouraged, and I want
to tell about my own experience.

Um, Sini, when you first hired me,
you said, you know what, uh, bite your

tongue, be prepared and get ready.

And what happened was
that you supported the.

The writing of a proposal that
eventually became an IMI, uh,

proposal, and IMI EPA came out of that.

IMI EU Pearl came out of that.

Other things came out of it.

None of that would've been possible
without a champion who happened to be my

boss within a farm r and d organization.

And I'm absolutely convinced there
are peril situations elsewhere.

That's number one.

Number two, our uh, boss, uh, Dr.

Paul Stoffels used a phrase
saying, you take the risk.

Husseini Manji: Mm-hmm.

Mike Krams: I take the blame,

Husseini Manji: Mm-hmm.

Mike Krams: that was an
extraordinarily liberating statement.

Basically saying, Hey guys,
I want you to take risks.

Again, I'm convinced that
similar, perspective exists

everywhere across a pharma.

And so that begs the question then.

Now, why is it that we are in
such a conservative environment?

part of it is that the infrastructure
that we've created, is very myopic.

you have compound development teams.

Scott Berry: Yeah.

Mike Krams: We don't have the
team that solves psychiatry.

Patient problem.

Looking at the relevant pathway
that's underlying different,

diseases that's a problem because the
incentives that exist and the whole

infrastructure is really organized by
compound asset rather than, biology.

The other thing in, the pharma r and d
environment is everything is extremely.

time-line driven.

that lends itself, again, to a myopic
perspective where we are rewarded for

achieving something in the near term.

But maybe that near term achievement,
starting a particular trial or

having lots of patients included in
a trial in a short period of time

are actually is not really meaningful
in helping us to get to the end game

what it takes there.

Are individual protagonists for
innovation who bridge the gap

between these pressures that exist?

Time pressures, budgetary pressures, the
difficulty of synchronizing different

utilities within an organization and the.

Invitation from senior
management to be innovators.

one last point in my experience, and
again, supported by Hui and others,

all the interactions that I look back
at with health authorities have been

incredibly valuable learning experiences.

So it is absolutely not the case that
health authorities and regulatory.

Experts are conservative by nature.

Absolutely not.

have such an insight broadly
that can help, the right path.

So I would say, the patient-centric
perspective will lead us to bridge

the gap around some challenges exist.

But the invitation is there to
be innovators and the type of

GBM Agile model that we have,
I would think is a good setup.

Husseini Manji: Great.

Um, could I just comment
on, um, what Mike said?

Scott Berry: Sure.

Husseini Manji: Yeah.

Great.

So, so I think, I think, you know, Mike's,
um, comment sort of, um, reinforced to me

why we get along so well and why we're so
much, you know, we're mind melted because

everything he said I'd agree completely
with, and that just amplify a few things.

So as this, um, one of the key
tenants as part of this, um, UK mental

health goals program is actually
a patient industry partnership for

exactly the reasons Mike mentioned.

You know, we want to embrace patients,
learn from them, and, you know, sometimes

they tell you that, you know, if you, you.

You, you as a, you know, medication
developer might think this is the

biggest unmet need, but actually
Prozac is okay for my depressed

mood, it's my lack of motivation, my
inability to go to work, et cetera.

So to have the patient sort of, um,
educate, for lack of a better word,

industry, this is what I really need.

Um, I.

The second thing is that help industries
sort of, you know, talk to patients about,

you know, there might be some things that
we know is a big problem for you today.

Um, and say for example, COVID, you know,
induced a lot of what we call brain fog.

But unless we, you know, right now we
don't even know what brain fog is, how

to measure it, what the target would be.

So it could be something we tackle down
the road, but unfortunately today's

side doesn't allow it us to do it here.

Coming back to what Mike
said and the patient.

Um, advocacy, you know, in conditions
like hiv, aids and many other conditions

really drove things and we think that
the same thing could be happening here.

They can indicate that I'd
be very happy to volunteer.

What Mike said about regulators is
completely my experience as well.

So with Rob Kiff, with Janet Woodcock,
with June Rain, who was the head of

MHRA, it's been exactly the same.

They want to be, you know,
sort of more agile, get things

to help patients, et cetera.

They need to obviously have a
bar for the evidence, but they're

very willing to work with you.

So the last thing I'd say is, once
again, I would agree with Mike in

terms of how this could be done.

So I think some sort of,
you know, public-private

partnership, so, you know, um.

You may know that a acne, the Alzheimer's
Disease Neuroimaging Initiative would've

been one of these great success,
um, stories where, you know, we were

able to collectively identify people
who are on their way to dementia.

And based on the rigor with
which things were done, there's

actually now a plasma marker.

Um, plasma two 17 phospho, that
is looking amazingly good, but you

wouldn't have been able to come up with
it unless you were able to have this

large longitudinal study, et cetera.

So we've got this initiative in the
UK and we're actually talking very

closely to the French government,
to the German government, and

in fact, for many years while.

I was at j and j, I was the co-chair of
the foundation for the NIH Biomarkers

Consortium, the Neuroscience Group.

So I think there's a distinct
possibility that, you know, sort

of, if we frame this correctly, I.

We can get both public and private, and
most importantly, patient stakeholders

to come together, you know, from,
you know, the biopharma companies.

Not everyone will join, but if XX
number of join, again, you know, Mike

referred to our boss, Paul Stoffels.

One of the things he's really also
championed is what's happened in the

semiconductor industry where things have
moved forward so well that if you're not.

Part of this consortium, you
actually get left behind because

all the advances happen here.

So I think in industry there
may be some early movers.

You know, my hope is that
companies like j and j and Lily

and BMS and Abby, et cetera.

We'll join early, but then based on the
success, others will want to join as well.

And I think we can, we can pull
this off if we put the right people

together and the right infrastructure.

And the last thing I'll mention, and
you don't wanna over promise, so I think

that's sometimes, you know what sort
of is bad people, you know, say, claim

we're gonna cure world hunger with this.

No, we're not.

You know, we're in an early stage.

We need to think systematically,
but this is how we'll go about it.

Scott Berry: Uh, that's, that's fantastic.

I, I.

Seems incredibly promising,
seems very doable.

And, uh, uh, I think Dr.

Manji, you're the one to make this happen.

So we hopefully will come back with
some updates on what this effort

looks like and, uh, uh, hussei, I
wanna thank you tremendously for

joining us here, uh, in the interim.

Husseini Manji: Well, it's
really been my pleasure.

I think that you can probably
tell from my comments.

I really do feel we're at an inflection
point, and if we can come together as a

society, we can make a real difference
for patients because unfortunately,

the suffering today is staggering.

Thank you.

Scott Berry: Yeah.

Mike Krams: Thank you.

Scott Berry: thank you very much.

Mike Krams: Thank you.