Path 2 Parkinson's Prevention with Drs. Simuni and Wendelberger

In this episode of "In the Interim…", Dr. Scott Berry is joined by Dr. Tanya Simuni, Arthur C. Nielsen Jr. Professor of Neurology and Director of the Parkinson’s Disease and Movement Disorders Center at Northwestern University, and Dr. Barbara Wendelberger, Senior Statistical Scientist at Berry Consultants. The conversation focuses on the Path to Prevention (P2P) platform trial—an international, multi-arm prevention study in Parkinson’s disease targeting participants defined by biological markers, specifically alpha-synuclein pathology, prior to clinical diagnosis. The discussion covers the PPMI cohort, trial operational and statistical structure, the rationale behind biomarker-driven inclusion, and the use of Bayesian platform trial design.

Key Highlights:

• Parkinson’s disease pathobiology and risk: genotype-phenotype variability, multi-system involvement, and the central roles of age, environment, and genetics.
• Michael J. Fox Foundation’s PPMI cohort: 4,000+ participants, prospective longitudinal biomarker and clinical data, high participant retention, enabling study of early Parkinson’s.
• P2P platform structure: multi-arm design, two-stage randomization with shared placebo group, integration of non-randomized PPMI cohort in Bayesian analysis for improved inference.
• Inclusion criteria: prodromal population biologically defined by CSF alpha-synuclein seed amplification and dopaminergic imaging (DAT-SPECT), highlighting regulatory nuances.
• Dual primary endpoints: biomarker (DAT-SPECT) and clinical (MDS-UPDRS Part III), 24-36 months follow-up.
• Commitment to public data sharing in line with the Michael J. Fox Foundation’s open science philosophy.

For more, visit us at https://www.berryconsultants.com/

Creators and Guests

Host

Scott Berry

President and a Senior Statistical Scientist at Berry Consultants, LLC

What is In the Interim...?

A podcast on statistical science and clinical trials.

Explore the intricacies of Bayesian statistics and adaptive clinical trials. Uncover methods that push beyond conventional paradigms, ushering in data-driven insights that enhance trial outcomes while ensuring safety and efficacy. Join us as we dive into complex medical challenges and regulatory landscapes, offering innovative solutions tailored for pharma pioneers. Featuring expertise from industry leaders, each episode is crafted to provide clarity, foster debate, and challenge mainstream perspectives, ensuring you remain at the forefront of clinical trial excellence.

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.

I am joined today by a couple
of really interesting guests

and a really interesting topic.

I'm your host, Scott Berry.

I should do that, and I'm
joined today by Tanya Uni.

She's the Arthur C.

Nielsen Junior Professor of
Neurology and the direct.

Of the Parkinson's Disease and Movement
Disorders Center at Northwestern

University Feinberg School of Medicine.

She is an expert in the design and
implementation of Parkinson's clinical

trials focused on disease modification
in the lead, author of the new Biological

definition and staging framework
for neuronal synuclein disease.

We, we'll talk more about
what, what, what that is.

Uh, and she serves on the
leadership team of the Michael J.

Fox Foundation, sponsored PPMI study,
and it's the largest Parkinson's

disease biomarker initiative.

Uh, and we're gonna talk
much more about that.

And we're gonna talk about platform
trial that has been generated, the first

platform trial that has been generated.

From that.

We may, we may have more,
uh, also joined today.

By Dr.

Barbara Wendell Berger.

She is from, uh, here
at Berry Consultants.

She's a senior statistical
scientist at Berry Consultants.

She's been here nine years.

She got her PhD in statistics from the
University of Wisconsin where she worked

on statistical and computational biology.

And she focuses a good bid on
neurodegenerative diseases, innovative

trial designs within neurodegenerative
diseases and disease progression modeling.

She's the scientific lead
for Barry Consultants in

our work with the Michael J.

Fox Foundation and working with with
Tanya on the different projects.

And so welcome both of
you two in the interim.

Barbara Wendelberger:
Yeah, thanks for having us.

Tanya Simuni: Thank you for inviting us.

Scott Berry: So let's, um,
let, let's get into this.

First, I, I want to talk about the
P two P platform trial, but I think

it, it takes a bit to get to that.

And so first, I, I, I've not
done much in Parkinson's disease,

but what is Parkinson's disease?

Tanya, can you give us the, the,
the, the quick intro that we

need for Parkinson's disease?

Tanya Simuni: Absolutely.

Uh, 32nd seconds Parkinson's primer.

Parkinson's is the second most
common neurodegenerative disease

after Alzheimer's that is manifested
by the clinical TR triad of

slowness of movements, particular
muscle stiffness and resting trem.

That is the clinical phenotype.

That drives clinicians'
diagnosis of Parkinson's disease.

However, Parkinson's is much
more than a motor syndrome.

It in encompasses a spectrum of
cognitive manifestations, specifically

with the progression of the disease,
behavioral manifestations, impairment

of a autonom nervous system.

Sleep dysfunction, so it's
truly multi-system disorder.

So far, what I've told you in
my 32nd primer is the clinical

syndrome of Parkinson's.

I haven't told you what
causes the disease.

We don't know that, and I have not told
you what is the underlying pathology of

the disease, which is absolutely relevant.

The underlying pathobiology of the
disease is that there is a progressive

loss of cells in, uh, midbrain, uh,
structures of substantial nigra and

other related neurons that translate
into progressive loss of production of

the neurotransmitter dopamine, which is
responsible for the motor manifestation.

There is much more than dopamine
loss, but this is the primer.

And the last point is based on what
I've just said about underlying

pathobiology and clinical syndrome,
what is obvious from that is that

there is a long lag in between
onset of disease path biology, and.

Progression of it to the point
when someone shows up in the

physician's office with the first
complaints of their symptoms.

And the reason why I'm highlighting
that because it gets us to P two P,

their opportunity to intervene before
someone develops the classical phenotype.

Sorry, for more than 30 seconds.

Scott Berry: No, no, that was great.

Okay, so you, you talked about
the, the clinical symptoms, the,

the, the phenotype that shows up.

I, I, my.

It, it seems like a different
kind of disease, that there may be

multiple ways in which somebody,
uh, uh, develops Parkinson's.

Can it be a genetic disease potentially?

Can it be, uh, um, environmental
things potentially that have caused it?

Uh, you know, we've talked about,
uh, I I've heard potentially

that, you know, at, at.

Agent Orange in military settings or other
things can trauma potentially cause, so

there's lots of ways in which you can,
you can come down with Parkinson's.

Tanya Simuni: Great questions.

Uh, as I've alluded, the
course of Parkinson's remains

unknown.

We carefully indicate that it is
interplay between environmental

courses and under that umbrella.

It's toxins exposure.

It's trauma and multiple
other unknown factors, right?

And genetic predisposition.

If you look at the Parkinson's population
at large, approximately 10 to 15% of

individuals carry gene that is known one
of the genes, right, that are known to

be associated with increased risk of.

Parkinson's.

Not every carrier of a particular
genetic variant will ever in

their lifespan develop Parkinson's
clinical disease because the word

is penetrance ability of the gene to
manifest with a clinical phenotype.

The penetrance of a number of
those genetic variance is low.

But getting back to your question.

It is interplay between
environmental and genetic courses.

There has been tremendous amount
of research in both domains.

There has been specific interest
in genetic courses because that is

something tangible that we can put our
hands on and translate into targeted,

personalized therapeutic interventions.

The one important factor that I
haven't mentioned so far is age.

Out of everything that I've told
you, the highest risk factor is age.

As any other neurodegenerative disease,
Alzheimer's disease, Parkinson's disease,

the prevalence of the disease increases
exponentially with the age of the disease.

Scott Berry: Hmm.

Okay.

So you described the, there's
so much that we don't know.

Uh, about Parkinson's, hence the,
the, the work that the Michael J.

Fox Foundation is doing in, in
understanding Parkinson's and the

development of the Parkinson's
progression markers initiative.

PPMI project, which is a precursor
and a current cursor, is it

certainly related to P two P?

So what is the, what is PPMI?

Tanya Simuni: PPMI is a seminal, largest
prospective observational study that was.

Launched by Michael J.

Fox Foundation back in 2010 with
a primary objective to validate

biomarkers of the disease progression.

Why such a huge investment
into that question?

Because the primary objective
of the study is to enable

higher success of the studies.

Specifically aimed at disease
modification, slowing progression of the

disease, and despite, in 2010, it was
about 20 plus years of trying by now,

it's 35 years of trying to and testing
multiple molecules and interventions

for slowing disease progression.

We still have not reached that pinnacle.

Scott Berry: Hmm.

Tanya Simuni: again, to summarize, it
is the study that started recruiting

back in 2010, individuals with newly
diagnosed Parkinson's disease, healthy

controls, later added populations, genetic
Parkinson's disease, and importantly

for the rest of our discussion.

What is called prodromal population.

People who do not carry diagnosis
of Parkinson's disease, but have

features and traits that we know from
epidemiological data, increase the risk

of development of Parkinson's disease,
and all those individuals are followed

by uni with a unifying structured
protocol of the assessments that include.

A plateau of the clinical assessments,
which are the traditional or potentially

endpoints for the clinical trials, but
mostly importantly, deep biological

characterization of the individuals

Scott Berry: Hmm.

Tanya Simuni: with measures, assessing
dopaminergic, uh, function and

collection of, and number of biofluids.

So that as the science develops,
uh, with the biomarkers, there

were samples collected that
those biomarkers could be tested.

And my last kind of statement would
be, as I have said, for years, it

was collection of the data samples
that actually since probably 2015.

Every single disease modification study
that has been launched by industry used

PPMI data to model their studies, design
disease progression, eye sample size, what

population to recruit, but in the early
2020s, really between 2022-2023 Major

breakthrough was made in Parkinson's IE
development and validation of a biomarker

of underlying synuclein pathology.

Synuclein is the protein that
aggregates in those vulnerable

cells and all the data supports.

While we are not making the statement
that, synuclein aggregation.

Is the solo cause of the
downstream cascade of the disease.

All the data supports that
it is the major contributor.

So for the first time in Parkinson's
history, we actually are able to

measure and assess biomarker of
underlying core disease pathology.

Scott Berry: Okay.

So, uh, a lot there.

First of all, uh, do you know
the, do you know the number of

individuals, participants that
are part of the PPMI, uh, study?

Tanya Simuni: I do exactly.

As of last week, we have hit, um,
4,000 individuals recruited in PPMI.

Scott Berry: Okay.

Tanya Simuni: what is important
is that retention of the

participants is remarkable.

Again, I've already said that, uh,
the study was launched in 2010.

Initially the participants were asked
to contribute the data for five years,

but the study evolved over the years,
and we have a number of participants who

are still in the study now, 15 years.

Wow.

Scott Berry: Hmm.

Yeah.

So this this incredible effort we have.

We have this disease where we understand
the phenotypical clinical symptoms.

You said the second most common
neurological disease, but we don't

understand a great deal about how people.

Get to that point.

So Michael J.

Fox Foundation creates this
amazing longitudinal study

to study, uh, individuals.

Many of them coming in, um, maybe
have certain risk factors, family

members that have had Parkinson's.

And so they go into this, this study
and following them probably now

we, we, we have many with 10 plus
years exposure, and you are getting

biomarkers on these individuals.

You're getting.

Clinical outcomes of them.

Now, despite this being a very common
disease, it still must be reasonably

rare for these individuals to then
become symptomatic, but this incredible

study to learn about the disease.

And now that that study continues,
and, and we wanna highlight the, the,

the work that the Fox Foundation has
done in this, in understanding the

disease, and you high highlighted that,
that pharmaceutical companies that

want to go into Parkinson's disease,
this is become an incredible engine of

information of, of, of study design.

The value of this is, is incredible
and the, that what they've done.

But they want to do more now.

And I'm gonna come back to this
alpha synuclein part I, which I

don't understand a great deal of it.

But now the notion is you've got this
longitudinal cohort, maybe we can learn

about treatments to slow prevention.

So Barbara, is this the, the notion
behind path to prevention P two P study?

What, what?

What is that?

Can you tell me what that is?

Is.

Barbara Wendelberger: Yeah, so.

The path to prevention study
that we've been working on, um,

for the past number of years is
a global perpetual multicenter,

multi regiment clinical trial.

So it's a large platform trial where
we're studying, um, the safety and eff

and early efficacy signals of various.

S possible therapeutic options.

And as Tanya has mentioned, it very
much targets this early population,

um, of alpha synuclein disease.

So we're, we're really trying to
target participants who have some

early signs of Parkinson's disease,
um, to see if we can really, uh,

focus on prevention and identifying
early signals for therapeutics.

Scott Berry: So the platform part
of this, just to, to sort of make

it clear, is that there will be
multiple regimens in this trial.

I have multiple treatments simultaneously
being investigated, common controls.

Uh, within this, uh, do you have, is
the plan to have placebo controls.

Barbara Wendelberger: Yes.

Um, so there are placebo
controls for the different, um.

A shared placebo control for
these different regimens.

And additionally, we are planning to
leverage information from non-randomized

participants from the PPMI study.

So we have participants who would be
eligible for P two P, um, but don't

choose to enroll into the platform.

And so that information on those
non-randomized control participants.

Is built in to the analysis.

In addition to that shared, uh,
randomized control information

within the platform trial.

Scott Berry: Yeah, so that, that,
I want to come back to that.

That's such a neat.

Um, incredibly valuable scientific
aspect of this to understanding whether

any of these treatments are beneficial.

But I want to come back to the
patient population and maybe

I, I shouldn't even be calling
these patients, but participants.

Uh, but I think it comes back, Tanya,
to what you were describing and you

were the, uh, lead author of a paper,
a biological definition of neuronal.

Alpha synuclein disease towards an
integrated staging system for research.

So I think this is an important
part of the P two P trial

and who the participants are.

So come back to this idea
of alpha synuclein disease.

This is, uh, a marker that was, uh, I, I
don't developed but discovered in PPMI.

Which you're able to stage
the risk of Parkinson's for

individual based on this biomarker.

Tanya Simuni: Let me
clarify a couple points.

Uh, alpha-synuclein.

Is, you are correct, but
let's walk through that.

Scott Berry: Yep.

Tanya Simuni: So Alpha Sinin is the
innate protein that plays a number

of physiological roles in the cells.

It is present not only in the cells of
the nervous uh system, it is present

peripherally in pathological state.

It aggregates and.

In aggregated form, it becomes toxic to
the cells and interferes with a number

of, uh, core, uh, cell, uh, functions.

And as I have said, all the data supports
that it is one of the key, uh, reasons

for the progressive dopaminergic cell loss

for the last 150, a hundred years, right.

Clinician made the diagnosis of
Parkinson's pathologist verified

clinical diagnosis based on looking
at the tissue, autopsy tissue, post

someone's death, and seeing two key
variables, loss of dopaminergic neurons

and Lewy body inclusions in in the cells.

And the major constituent
of that is Alpha sin cle.

What was the breakthrough is, so that
is clinical diagnosis when someone

lives pathology, confirmation when
someone passes and nothing in between.

So the major breakthrough is that
there was development, uh, of the

biomarker of nucle pathology based on.

CSF sample using the technology of
seed amplification ppp, Michael J.

Fox was instrumental in
supporting the research leading

to development of the biomarker.

And PPMI is the largest cohort
that validated the biomarker.

Now, from the biomarker to
definition of the population.

The objective for P two P,
the objective is to test the

therapeutics before people develop
the classical Parkinson's phenotype

diagnosed of Parkinson's disease.

That population currently is
labeled as prodromal population.

Prodromal is not well
regulatory, accepted term.

It is very nonspecific.

So what the biomarker discovery allowed
us to introduce biological definition

of the disease in living person, right?

So we can test the biomarker
CY nuclear pathology.

And based on that we have postulated
that anyone who has positive.

Biomarker of synuclein.

Pathology has neuronal synuclein
disease independent, whether they

give the clinical phenotype or not.

The next

uh, core biomarker is biomarker
of dopaminergic dysfunction,

which today is widely available.

Dead spec scan.

So these are the two core
biomarkers that are being tested

in that pre-class diagnosis.

Diagnosis population.

And if people are positive, they
have neuronal CY nuclear disease.

They have what we have described
as nuclear disease, stage two B.

And provided that they meet other
inclusion criteria and do not have

key exclusion criteria, that is the
population that we are targeting.

So the novelty, the first platform
study in this prodromal population, the

first time to recruit the individuals
based on biologically defined

population and not much less specific.

That phenotype of prodromal population.

Scott Berry: Hmm.

So that, uh, that's fantastic and,
and I, I assume at this point.

Uh, and, and I, I do, uh, create the
analogy to Alzheimer's and about, you

know, Alzheimer's, uh, with amyloid.

And is, is amyloid a, uh,
correlation to disease?

Is it the causal pathway of all of that?

You, you refer to this as staging,
which I assume means that it's certainly

correlated to developing Parkinson's.

It's on the pathway, but we don't
know if altering that would alter.

Whether you're going to get
Parkinson's, whether you could slow

the progression of Parkinson's.

That's a huge scientific question
moving forward, I assume.

Tanya Simuni: You are absolutely correct,

but.

Biologically defined population is
an essential prerequisite, right?

As sta statistical experts, you
know that the key, uh, enemy in

the studies is variance, right?

And recruiting individuals with
variants of underlying biology.

Negates our ability to
test the hypothesis.

Specifically if the therapeutic is
targeting that underlying product.

It doesn't make sense to test
amyloid targeting therapists in

people who are negative for amyloid,

right?

History has clearly shown that

it doesn't make sense to test nucle
targeting therapeutics in people who don't

have underlying, say, nuclear pathology.

Scott Berry: Hmm.

So, so part of this, the variance
aspect of this, if we went out

and said we want to do a treatment
for the prevention of Parkinsons.

And we don't have this knowledge of
synuclein disease, uh, synuclein staging.

We might need to enroll many hundreds,
thousands to get positive cases out of

a placebo, out of a natural history.

But now to be able to enroll this
prodromal population that are

positive for synuclein disease.

This prodromal population, we've
enriched it for much more likely

to develop it, which enables us
to en to to do this P two P trial.

Uh,

Tanya Simuni: Uh, all accurate?

Yes.

Scott Berry: so Barbara now embedded
within this whole structure.

We've got these, this
prodromal population.

And give me a little bit about the, the,
the statistical scientific structure

of the clinical trial embedded within
this whole structure, uh, uh, of this.

And let, let's assume, let the status
of this right now, as you're not

enrolling any of you, you're not
randomizing any patients right now.

Is that right?

Tanya Simuni: That is correct.

Scott Berry: Okay, so, so Barbara, let's
assume you get three treatments in here

that are interested in this, this, this.

Stage two B, this prodromal population.

What is the scientific structure
of the trial look like?

Barbara Wendelberger: Sure.

So the trial is this randomized
entity within our larger, um,

non-randomized cohort and.

If we have three different
arms enrolling, we're following

patients for 24 to 36 months.

Um, so we have at least 24 months
of follow up on each participant.

Um, some of the earlier participants
we do follow longer, so that's

the, the up to 36 months.

Um, we're collecting data.

We have multiple primary
endpoints, so we have a biomarker

endpoint and a clinical endpoint.

Um, the biomarker endpoint
measures this dopaminergic

dysfunction that Tanya's mentioned.

Uh, so that is the DAT SPECT imaging.

And then we also look at a clinical, uh,
uh, endpoint, which is M-D-S-U-P-D-R-S

part three, um, which is a very common,
uh, endpoint in the Parkinson's space.

And so that is looking at, I
believe, motor dysfunction.

Tanya Simuni: You are correct.

Barbara Wendelberger: Yes.

Um, and so.

What we're doing is with these three arms,
a participant enrolls in the trial, we

have a two stage randomization system.

Um, so first the participant is equally
randomized between the available regimens.

So in this case they'd be
randomized one to one, to one

into either regimen A, B, or C.

And then within that regimen we
have a K to one randomization.

Um.

Which is the number of regimens.

So in this case that's K is three.

We have three actively,
um, randomizing regimens.

And so within regimen we have
a three to one randomization of

active treatment to placebo control.

Um, and what that allows us is within the
randomized population to have a one-to-one

comparison of an active, the active
treated group to our shared placebo,

which is shared across that A, B, and C.

Um, regimen and, uh, success in
this can be a positive outcome

on either the biomarker endpoint,
the clinical endpoint, or both.

Scott Berry: And, and roughly,
uh, a sample size for, for an arm.

Barbara Wendelberger: Yeah, so
we're, we are looking at 125,

um, participants in an active.

Uh, on the active therapeutic.

Um, so it, you know, the, the
controls vary a little bit, but

125 to each active treatment.

Scott Berry: Okay, so if, if, if
three arms were able to start this

simultaneously, we have 125 on a 125
on B, 125 on C, roughly 125 placebos.

At the same time, I want to come
back to this fantastic aspect of

You You have individuals that are
part of the PPMI greater effort.

Um, you, you, you presumably are going
to have before their randomization, their

characterization of these individuals,
but then they're randomized and I'm sure

you're collecting more, uh, regular,
uh, collection for these individuals.

But you also have somebody that
might be eligible for this trial.

Continues to have their data collected in
PPMI and grants the right for their data

to be analyzed, uh, for this that could
be used to reinforce your control arm.

And the whole huge thing for these
1 25 is what would've happened

if they didn't get the drug.

And you've got this
additional information.

This is such a unique set of data to have.

Within the trial.

So you're going to use those to
enhance the control, presumably.

Barbara Wendelberger: Correct.

Scott Berry: That's that, uh,
that's fantastic in the, this whole

embedded aspect within the learning.

So let's think about what would happen
here if we didn't have the Fox Foundation,

PPMI and a pharmaceutical company, first
of all, they wouldn't necessarily have.

This.

Without this, we wouldn't have known,
perhaps stage two, you wouldn't be

able to do this for a pharmaceutical
company to go out and find these

stage two patients would be incredibly
challenging, I imagine, Tanya?

Tanya Simuni: jump in.

You are absolutely right.

Probably I would put it even
more pragmatically in the

current state of affairs.

That study will not be feasible

Scott Berry: Yeah.

Tanya Simuni: outside of PPMI.

One of the objectives of P two P is to
develop the learnings and bring them

to the industry community to make such
STU studies in the future reality,

because obviously disease prevention,
therapeutic trials are the pinnacle.

The Holy Grail, we

need good drugs.

We need the right population.

We need the right outcomes.

Simple recipe, tough to get

the right cake baked

right.

Scott Berry: Yeah.

Yeah, so, so it essentially they
wouldn't have the ability to, to get

these patients, whether they'd have even
the knowledge of who they are, which,

which we now know the knowledge of this.

Um, it would be incredibly
challenging to enroll that, that

patient population, um, but then.

E even in the simple case where
they could find these patients,

they, they all individually
might need to enroll 125 and 125.

And so we're immediately, it's 250
more patients, uh, uh, for, for the

community of these three trials to
be done, uh, within this setting and.

Individually, when pharma A runs
their trial, that information

is kind of cordoned off.

It's in a study.

We don't get access to that data.

We don't really learn from it.

All of this data goes back into
this incredible learning atmosphere.

So this isn't just does drug a work.

This is continuing to contribute
to our understanding of the

biomarkers and progression and
the behavior of the disease.

I.

Tanya Simuni: You are absolutely right.

Um, it is eco obviously, if.

One of the tested therapeutics shows
needs their endpoints, either primary

or secondary, and which provides the
justification to, for the individual,

uh, company to move a adhere with
a further development of the drug.

That would be terrific, but independent
of assessing efficacy of the therapeutic.

All the learning aspects that
you have just indicated, right.

And bringing the data to the, uh,
community, uh, for further learnings

right, will advance ability to,
of the first of all, advance the

science and advance the ability
to implement future studies.

Yes, Barbara has indicated what
are our components of multiple

primary endpoint, uh, approach.

These are the best.

Based on the modeling and extensive
work of the Barry, uh, team

that I really want to highlight.

Barbara, Amy Crawford.

Uh, Cora, uh, Ellen, uh, right.

We've been working for three years by
now, and if people asking, what have

you been doing for all this time?

Right?

It takes a lot of time because
PPMI is a living study.

It's constantly, it's.

Adding participants.

Uh, we have new data.

We have new understanding of the
data that enriches our, uh, modeling.

So again, but the data will become
available in the public domain

as quickly as we can while the
participants are, are propagating

through the interventional arms.

The data that aligns with PPMI dataset.

Still will be available in the PPMI site

for the P2P data.

Once their arm completes and retires,
the intention is to make the dataset

again, publicly available, aligned
with overarching philosophy of the

foundation, advancing the science,
leading to better therapeutics for people.

Scott Berry: Yeah.

Yeah.

I, I, I mean, it's
stunning to think about.

The, the effect this has where we, we have
a number of trials in fully symptomatic,

uh, patients that have been diagnosed
with Phenotypical, uh, Parkinson's.

There's a number of drugs out
there to looking at U-P-D-R-S

as the primary endpoint.

It's, um, it's all of that.

But this has enabled us to move
into this prodromal population,

this incredible scientific machine.

Um.

Oh, is this something?

And, and I'll ask this as
kind of a bigger question.

Why don't we do this in,
uh, many more diseases?

Tanya Simuni: Great question.

Uh, Berry team, uh, has really
contributed and largely pioneered.

The concept of the platform studies
and now every meeting that we

go to in, at least in, uh, the
space of neurodegeneration, the

discussions in clinical trials
start with platforms, right?

Uh, and Bayesian approach
to the data analysis.

I always add, it is platform is
an incredible vehicle of studies,

efficiencies of smart studies, design.

It puts the vehicle to the charge
of having right, uh, cargo on top.

We need the right drugs.

Right drugs, right.

Population selection.

So to answer your question, why aren't
we doing that in other diseases?

Those are in development.

also depends, obviously
Alzheimer's is the frontrunner.

Uh, they have.

Major advancements in biomarkers.

They're testing the therapeutics and,
uh, the MCI biomarker defined MCI

population, but also in, as you well
know, in romal dominant, uh, Alzheimer's,

uh, uh, PRS asymptomatic, right?

So it requires, in order to move
that from observational studies into

therapeutic interventional studies.

we need maturity, uh, of certain degree
of maturity of the biology, right?

Uh, we need the infrastructure.

We need the investment.

And again, calling out the
foundation for being really

bold for supporting this initiative.

Scott Berry: Yeah.

Yeah.

Fantastic.

So, so Barbara, the, the Barry team has
been working on the trial design, uh, and

Tanya talked about, uh, Cora Allen Savita
and Amy Crawford working with you on this.

Uh, Ben Seville, who was previously
at Barry, did, did some work on this

as well, but you're working with a
data coordinating center as well,

Barbara Wendelberger: Yes.

Scott Berry: and who is that?

Barbara Wendelberger: Uh, that is
University of Iowa, um, and led by

Chris Coffey, so himself and his group,
and they have been just instrumental

in understanding what is in this data
set and enabling the work that we

have done in the trial design piece.

Tanya Simuni: Yep.

Scott Berry: Yeah.

Tanya Simuni: Chris is the chief
biostatistician for PPMI study.

And his, him and his team have been
supporting statistical analysis

of PPMI data since inception.

And you can be, you can imagine
4,000 individuals by now,

uh, 15 years since inception.

A lot of data,

Scott Berry: Hmm.

Tanya Simuni: a lot of
analysis, so again, huge credit.

Scott Berry: Yeah, so what, what
a fantastic scientific effort.

Um, and, and again, I want
to highlight the Michael J.

Fox Foundation for making all of this go.

Uh, and, and I, I'm going to be, um, uh,
crushed for saying this, but I believe

they have taken us back to the future.

Um, in this, and, and I know
I'm gonna be crushed for saying

that, but it's incredible effort.

So, Tanya, thank you
for joining us, Barbara.

Thank thanks for joining.

Uh, we will come back to this.

Uh, we, we can't not
have an update to this.

Uh, when arms start, we want to
know, and I know that this is a.

Aggressively happening
to, to add these arms.

Um, we, we wanna get an update on this.

We want to get an update on the
learning of, of Parkinson's disease.

But thank you so much for joining
us here, uh, in the interim.

Tanya Simuni: Thank
you for the invitation.

Would love to be back
a fan of the podcast.

Actually have it on my LI library.

Scott Berry: Ah, fantastic.

So you're the one.

Uh, wonderful.

Uh, and for everybody else, we
will be here in the interim.

Thank you.