The STEP Platform with Dr. Eva Mistry and Dr. Jordan Elm

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 to In the Interim,
this is our podcast of clinical

trial science, what's happening new
in the world of clinical trials, and

I have two wonderful guests today.

We are gonna talk about the step platform
and we'll talk about what that is.

But my two guests today, Dr.

Eva Misery, who is a, an associate
professor in the Department of

Neurology and Rehabilitation Medicine
at the University of Cincinnati.

Welcome Eva.

And we have Dr.

Jordan Elm, who is a professor
of biostatistics at the Medical

University of South Carolina.

And both of you are investigators
in the step platform.

Eva Mistry: Thanks Scott.

Scott Berry: So Eva, why don't you
tell me what is the step platform?

Maybe we'll talk a little bit
about the platform, what it is, and

then after that we can kind of go
back and say, how did we get here?

Uh, it's a, it's a, it's
sort of interesting story.

So what is the step platform?

Eva Mistry: Um, so step
platform is an innovative trial.

It's a platform trial.

Um, the aim is to understand what are the
best treatment strategies or combination

of treatment strategies that are.

Improve outcomes of acute stroke
patients who have a visible occlusion

in one of the vessels in their brain.

Um, and that can include device-based
therapies or medications, or just

strategies, uh, of usual clinical care.

So all of those questions are fair point,
um, uh, to study in the platform trial,

the platform is embedded, uh, within an
existing infrastructure of NIH stroke net.

So just to tell you a little bit, NIH
stroke net is an NIH funded infrastructure

of a network of hospitals across the
country, uh, that participate in, uh,

phase two and phase three clinical trials.

Um, again, those are NIH funded trials.

Space of stroke.

Um, so this platform is embedded
within that existing infrastructure,

uh, but is, is is studying population
of acute or sudden stroke patients

who have this specific type of
occlusion that's visible in their,

uh, in their brain blood vessels.

Scott Berry: Okay, so, so STEP is Stroke
net Thrombectomy, endovascular platform.

Uh, for, for the, the,
the acronym of this.

So Stroke net is a network of sites, uh,
that's existed before the STEP trial.

And then STEP is coming in and it's using
those sites and it's a master protocol.

It's a platform trial.

Okay.

Um, within that, we'll, we'll talk more
about what that means, uh, uh, within it.

And this is NIH funded, but this
is also public, private, um, uh,

in the sense of the questions that
get added within it, uh, in it.

So what is the.

The, the overriding goal of it clinically.

So, so Eva, clinically, what are,
what are we trying to do in step

Eva Mistry: Um, so just to kind of dive
in a little bit of the history, because

that is important to contextualize, um,
what we're doing in the platform trial.

So I wanna take you back to 2015.

That was the year 20 15, 20 16,
uh, when face of acute management

of stroke patients really changed
with this, um, therapy called

Endovascular Clot Retrieval, which
is a device-based therapy where a

virus is inserted through an artery.

Um, to kind of suck out or,
or engage and take out a large

blood clot from the brain.

And that really changed the
face of acute stroke management.

This was very, very, uh, efficacious
therapy that improved lives of patients.

Once these therapies were out and
tested, uh, and approved, um, we then

were grappling with lots of questions
that surrounded this treatment.

For example, how do you take
care of several medical aspects

surrounding this therapy?

For example, types of anesthesia
given during the procedure.

What is the blood pressure management?

After the therapy is given,
uh, we grappled with.

Expanding the population that is eligible
for this therapy because it was so

effective, the field wanting to offer
this therapy for more to more patients

than were studied in the narrow, narrow
clinical trials back in 2015 and 16.

Um, so from an NIH perspective,
this really opened a floodgate of

applications to NIH to to study
various aspects surrounding.

Uh, this therapy specifically in the
population of stroke patients that

have a vessel occlusion in their brain.

Um, so that was an impetus for NIH to
figure out novel and innovative ways

to, uh, not just fund more questions,
but also answer more questions with

limited patient population that we have,
uh, at our sites in the United States.

States to advance stroke care,
um, um, along all of these

facets, um, for stroke patients.

So both time and economic efficiency
was the impetus score, um, for

conceptualizing, um, designing and then
eventually funding the step platform.

Um, it is funded through a novel
mechanism at the NIH and INDS.

Call other transactional authority,
uh, which has been used to fund

other platform trials, both at NIH as
well as within the NI and DSB four.

Uh, and that allows the opportunity,
what you were alluding to earlier,

Scott, which is industry partnership.

So, um, uh, some of our industry
partners can come in and.

Still go through the usual peer
review process for the platform.

So this is not something kind of to
just use the infrastructure is not

just for somebody to come in and use,
but uh, for them to apply in a similar

manner as academic investigators would
go through peer review process for

their application and proposals for
clinical clinical trial questions.

It's still a single clinical
trial, but, uh, but their own.

Um, uh, you know, agents or
assets, things like that.

Um, and then once approved,
uh, they can use the platform

infrastructure to answer this.

So it is, it is quite novel in that sense.

Scott Berry: So the old way of doing
this might be, we have all these

questions now in stroke about in
whom do we use endovascular therapy?

Do we use drugs?

All of the, aspects around
this we, the NIH might be.

Stuck with funding.

Four or five, completely
separate questions.

The patients are all different.

The, databases are all different.

The data coordinating center,
and they can only run four.

So maybe integrating this all within a
single platform, common patients, common

infrastructure, maybe they can address.

8, 12, 16 questions, continual questions.

So this is actually incredibly
exciting and NIH feels like the

right place for this kind of thing.

So, Jordan, tell me a little bit about the
master protocol, and as these questions

come in, what does this look like?

Jordan Elm: Yes.

So, uh, just to add on to what,
what Eva was saying about, a

little bit about the history.

So back when, 2016 when, um, endovascular
thrombectomy was shown to be very

effective, it was shown only in
some very discreet, um, populations.

And so all of a sudden questions
were coming to stroke net,

which is stroke net is a, um.

It, it provides infrastructure, not just
for the enrolling hospitals, but also

for the clinical trial management, so
the data management, statistical design,

and the clinical coordination center.

And so basically what was happening
was the questions were coming in

and saying, Hey, we want to look
at it in this population, and, and

somebody else would come in with
a slightly different variation.

The nice thing about the platform trial
is that we're using a master protocol.

Um, and that allows everybody to come
to the table and have a common framework

of, of where we're starting from.

Um, we can add on, uh, um, different
aspects of the protocol if it, if

it is important for that particular
question, but it allows us to have

this, um, basic kind of, um, set of.

Schedule of activities, um, uh, activities
that each participant would, uh, be a

part of which, um, are common to many of
the things that we would do in the past.

Um, we kind of try to enforce,
you know, some uniformity, but

it oftentimes goes out the window
because you have different people.

Um, running each trial and they make
a strong argument for why it needs

to be done this way versus that way.

And so you see a lot of divergence in
the way that a trial is rolled out.

Um, and so the really nice thing about the
master protocol in my mind is just having

this uniformity, um, as a starting point.

Scott Berry: So the I as we sit
today, by the way, I, I should,

I should let everybody know that
I, I do work on this project.

I'm part of the design team,
so I've been involved in this.

But, uh, and I, and I'll ask a little
bit more about the structure of, of

the various teams and how, how, how
everybody gets along and how this works.

But the first three questions, I
think right now we have, sorry,

we may have four questions.

Uh, and a, a a within that,
that we're currently working on.

Um, maybe Eva, can you give a
brief description so our listeners

sort of understand what these four
questions and, and if I'm wrong

on the four, correct me on that.

Eva Mistry: Um, I think I,
it, I I think you're correct.

It, it is four questions, so I'll
just kinda walk you through how,

how this platform can, you know.

Happened over over time.

Um, so we started with the design
calls and Scott, you and the rest of

the team at Berry were obviously very
integral part of that design discussion

to put together the master protocol
that Jordan was referring to earlier.

And then we added the first layer,
which is what we call the questions or

assets to that master protocol from the
get go to kinda realize this, as well.

So that question was.

basically if endovascular treatment,
improves outcomes in two subsets of

stroke patients that were not studied
in the original 2015 and 2016 trials.

So the first subset was those patients
who have a large occlusion in their brain.

But relatively milder stroke deficit.

So they have a milder stroke, but
a large occlusion in their brain.

And does retrieving that clot with
device-based therapy improve outcomes?

And the second subset of population
was those patients that have

clots a little bit further away.

From the main branches of the
vessels that were studied in the

2015 and 2016 trial, we call them
distal or medium vessel occlusion.

so the second subset of patients
was those who have those distal

and medium vessel occlusion.

So that is where we started with
the first iteration from the get-go.

So we.

We came up with a master protocol and the
first, what we call domain that included

studying endovascular treatment versus
medical management in a randomized fashion

for these two distinct subset of patients.

Um, NIH then opened, um, um, uh,
publicly, um, uh, applications for

further questions to be added on the
platform trial we received several.

In fact, we've received over.

15 to 20 applications at this point, I
should say NIH, N-I-N-D-S has, um, and

it's a two stage review process, um,
uh, of allow or, or activating these

questions on the platform, if you will.

So in the first stage of review, we now
have three additional questions, if you

will, that are added to the platform
or maybe added to the platform if they

pass through the second stage of review.

The first one is studying
again, endovascular treatment

versus medical management.

Uh, for another subset of patients, which
is those who have cognitive impairment.

Um, so that is one question.

And then there are two other
pharmaceutical partnerships, uh,

of their, um, novel neuroprotective
agents being studied in a phase

two slash two three model for dose
finding and then efficacy trials.

So really exciting times.

We're excited to put these forward for a
second stage of review and um, hopefully

we can, we can add them onto the platform.

Scott Berry: Um, okay.

so there are currently these
four questions going on.

So a patient.

Could come in and the, EVT aspect of it
is you're trying to figure out who should

and should not get endovascular therapy.

You've identified groups where
it's incredibly effective, there's

an expectation in others it might
not be effective, and this is

really trying to figure out who
should and should not get it while

simultaneously there's a medical domain.

And patients that come in who get
endovascular therapy, the question

is, would a neuroprotectant
improve their outcomes?

And so that sits there.

so Jordan, I, love the statistical
or the scientific aspect of this

EVT expansion because it's very
different than almost every trial.

We do many trials.

You walk in and you say,
does is a better than B?

And we power it to show
A is better than b.

But here we expect that there's
it's differential in the patients.

We expect that for some that
EVT might not be better and some

EVT may be better within this.

So what we're really trying to do
is almost find the cut point or

find who does and doesn't benefit.

So statistically, this is
a very different trial.

Jordan Elm: Yeah, I, it's been a lot
of fun working on this with you guys.

I have to admit, just, conceptually.

This has very, been very new for me too.

In terms of what is the, what
baseline characteristics define,

who may or may not benefit.

we don't usually, design studies like
this, we usually, focus in on what is the

population that's most likely to benefit.

We only enroll them maybe something
slightly outside that range, and

then we test does it work, yes or no?

And then this is just very asking a much.

Different question.

And it's really getting at the
science because we really wanna

know, we think it's gonna work
for a very large population.

And instead of testing these small,
discrete populations one by one,

over time, we're starting broad.

and then we're asking the question, at
what point is it no longer beneficial?

And so we have this, lovely statistical
change point model that, that, Scott, your

team developed, which has really been cool
to be a part of, which helps to answer

this question along the spectrum of the
baseline covariate, which is continuous.

we can find two cut points.

One in which the, treatment endovascular
thrombectomy is better than medical

management, and then going up and
then a period in the middle where

maybe they're both the same and then.

We can also identify on the lower
end of that continuous covariate,

the point at which the medical
management is, potentially better.

So a very different design,
somewhat of a enrichment design,

but not in the way that, that reen
enrichment trials are, often done.

Scott Berry: So the adaptations in this
domain, you are enrolling, I'll, call it

a wide group of patients that we don't
know the answer to, whether EVT is better.

You're randomizing 50 50
endovascular therapy or best

supportive care medical management.

And as the trial goes, the
adaptations could be, we've figured

out it does or doesn't work in
groups and we stop enrolling them.

Announcements may be made.

Papers may be published where
we still enroll those where

we don't know the answer.

So it's, been fascinating where we're
simulating not the power to show EVT

is better, but the power to identify
who should and shouldn't, it's a

whole new sort of way of the trial.

So then the medical domain, Eva
is, um, there are two different.

Uh, uh, neuro potential
neuroprotectants within this.

So what does that, the
domain is the medical domain.

What does that trial or,
uh, a sub trial look like?

Eva Mistry: Um, so since the,
the endovascular treatment advent

in past few years, the field of
neuroprotectant, or in other words,

and it's a pretty umbrella term,
frankly, so I, without going into the.

Neuroscience is a what, what,
uh, neuroprotection means.

There has been renewed interest because of
the, um, the surety in the drug delivery,

uh, to the target area, if you will.

If you take out the blood clot, you
can be somewhat sure that the agent is

going to reach the stroke area that was
initially kind of blocked because these

are, these drugs are usually given.

Via intravenous, you know, routes.

Um, so that is a renewed interest in
the field to find if, if, if we can

find drugs that can help with the
recovery or slow down the death of brain

tissue that is associated with stroke.

Um, so then this iteration we have.

Two pharmaceutical partners.

Each of them have their
neuroprotective agent.

They're both very different in terms
of the mechanism and what they do.

Um, both of them are supported by
preclinical data, of course, in

fact, one of them is supported by
preclinical randomized clinical trial.

Through the SPAN network, which is
another NIH funded network of preclinical,

uh, clinical trials for stroke models.

So we're very excited to translate
that directly into humans.

So it's a nice pipeline, if you will.

And then another one has come up through
regular, you know, industry chains.

Uh, again, both are very different trials.

Um, the first and foremost, they're
trying to understand, uh, finding the

best dose of both of these agents.

Um, in the ideal world, in the pivotal
stage, we would want some sort of

either co-enrollment or a head to
head comparison to find out the best

intervention or the strategy as it
comes to neuroprotective agents.

But since both of these are in kind
of more phase two, uh, dose finding

stage, they're not going to co-enroll
or compete with each other and.

Of course berries have worked
with us closely to find an ideal

model to be able to do that.

So right now the aim is to find the best
dose based on, um, either, um, you know,

long-term functional outcomes or surrogate
outcomes that are earlier than that.

Both trials are a little bit different,
uh, but once we have found the best

dose with a pretty pre-specified
and robust go, no go criteria.

Uh, from a dose finding or dose selection
to a pivotal testing phase, um, uh,

that is, that is an exciting aspect.

Frankly, for me.

I would have to say that, um, the number
of patients available to test something

like this in the United States and the
number of sites that can participate.

Can sometimes limit us as clinicians
in the field where then we are just

competing with each other, uh, uh, to,
to kind of enroll these participants

in many, many trials that are going on.

But the number of participants
available are small, so this

kind of helps with some of that.

Uh, we have a lot of committed sites,
um, that are, that are committed to

seeing through these, uh, these trials,
including phase two development.

Scott Berry: Uh, nice.

So both of these neuroprotectants,
so these are not a, a, as

opposed to thrombolytic agents
or, or this, that, that they're.

The, the potential to improve
clinical outcomes, they're,

that that's the goal of both.

They're both doing dose ranging.

Uh, and they could both stop for futility.

They could both continue on to a
point where they try to demonstrate

clinical improvement on the, not
the 90 day modified Rankin score of

the, the, the, the clinical outcome.

Jordan, what does this look like
for a patient that comes in to the

medical domain in terms of their
randomization, in terms of even

having potentially shared controls?

When this, what does this look
like in the medical domain?

Jordan Elm: So we spend a lot
of time talking about that.

Um, ideally we would like a patient
to be, participate in as many

domains as they are eligible for.

there may be reasons scientifically,
however, not to allow, patients

to co-enroll in different,
Different aspects of the platform,

but within the medical domain,

there are, some differences in the two
designs in terms of the eligibility

population and so in which the, space
in which the patients are eligible for,

both those patients will essentially, if
they're randomized to the control group,

they will serve as a shared control group.

if they're only eligible for one or
the other, they will not, participate

in that pooled, control group.

So it gives us a little more,
flexibility, in terms of patients

essentially coming in and being
eligible for more treatment groups.

and so they're getting, we're
having shared control, so there's

not, there's a lower likelihood
of them getting a control.

And that's a little bit of a pro,
I think as you're, thinking about

enrolling in a clinical trial.

And then, we also can pull those controls.

So there's the efficiency
that we get from that.

Scott Berry: Yeah, so it is in another
model if each of these sponsors

were running trials separately.

Somebody randomized to placebo
informs that trial, that one question.

Now that patient randomized
to placebo might be used by

both pharmaceutical companies.

We can enroll less placebos
globally across all of our

trials, which is a stunningly.

Nice aspect of this, platform

trial, you said randomized
to other domains.

So it could eventually be that, that
where here there's the medical domain does

being randomized, uh, to a neuroprotectant
help and they're asking that.

But they could be randomized
to endovascular therapy

initially and asking the question,
was endovascular therapy good?

And then that patient's also
contributing to whether the

medical thing given was good.

Eventually, this could be, you know, blood
pressure control, rehab, uh, multiple

aspects of their care as evil laid out.

The whole goal of this is to
improve the, the, the whole.

Aspect of the medical care this
single patient contributes to multiple

domains is is just incredible.

Jordan Elm: And, and I will say that's
a little bit of a different idea than.

Um, uh, you know, historically
we think of each clinical trial.

Let's control everything.

And we are not gonna allow any
participation in external clinical trials

while we're doing this clinical trial.

And this, uh, framework kind of throws
that upside down and puts it on its head.

And the idea being is that it would be
better to randomize to something that

they would have as background care.

Um, anyways.

Um, than just allowing
the background care.

So I, and then we can control
for that in the model.

We can put interaction effects to
kind of look at that specifically.

So I think it does give us a lot
more flexibility than what we

would maybe traditionally do.

Um, I, I.

Scott Berry: Yeah.

Yeah.

Very exciting.

So this is, right now, there's the four
questions that they're still, this is

a continual process of people applying

questions to this.

What does that look like?

Uh, what, what, uh, Eva,
what's the overall structure?

Or Jordan, what's the structure
of this and how does that work?

Jordan Elm: so there is a, um, a.

Uh, a funding opportunity
announcement, which is public.

Anyone can apply to it if they
have an idea for the platform.

Um, the first, um,
application is very simple.

It's just essentially the science,
um, the science justifying why it,

uh, is important to be studied.

They don't have to come with a design.

Um.

Once the science is peer reviewed
and, and essentially vetted to be

appropriate for the platform, um, it
comes in and, and they begin to work

with the step team to develop a full
design, um, to get integrated in with

the master platform, um, to develop
their pla uh, their protocol, um,

sorry, with the master protocol, um,
to get, um, their protocol appendix.

Uh, to the master drafted and, um, put
together a, a full, uh, application,

which then goes back to peer review,
um, to approve it for, um, uh, for,

to be part of this, uh, this platform.

So that's, that's the general process.

Eva Mistry: I had a couple of things,
which is, you know, it's good to clarify

some efficiencies that we frankly,
kind of think are NIDS colleagues.

Um, in thinking about this,
given that this is the other

transactional authority mechanism.

Uh, there isn't really a a, a
binding timeline for review.

It doesn't happen three times a year.

The review can happen once
there is a pile of applications.

So it's kind of an iterative process
and, and potentially faster than, than

a typical NIH review process that's
bound to three times a year cycle.

Um, even though there's two stages.

Theoretically it's a, it's a faster kind
of review and approval process, and again,

it can be a bit iterative where reviewers
raise certain concerns and you can kind

of go back with, with changes and comments
and, and get that reviewed pretty fast.

Um.

Which is exciting.

And then, um, in the same manner, the
industry partnership is really interesting

as well, where the ROA that Jordan
was referring to earlier allows for

industry partners to apply themselves.

So they now don't need an attachment
with, say, a university or a

academic PI or anything like that.

The industry partner themselves
can be the leader of their question

and work in partnership with.

Step, um, especially if they're bringing
on in some of their own support, um, in

terms of finances and things like that.

There can be a joint funding model also.

So there's a lot of efficiencies
and, and innovative, um, things in,

in terms of, uh, funding models.

Scott Berry: Yeah, it's,
it's, it's fascinating.

As somebody that's sort of on the
design side, we, we, I, I know

this process is going on, and at
some point it moves into this.

Interaction with the design team about
how would this fit in with everything?

Can we design this section of it?

And we've had four so far, and now
there's word of maybe two new questions,

two or three new questions coming in.

Jordan Elm: Yes.

Two more questions coming in.

Um, and it's just gonna
be an iterative process.

Hopefully we'll continue to
get people that apply and

get added into the platform.

Scott Berry: So where, so the listeners
may be interested in where we are on this.

Have we enrolled a patient in Step?

Eva Mistry: Yes.

In fact, we've enrolled 17, 18 patients
in step, in that first domain that

we were talking about in avascular
treatment versus medical management.

I'll maybe highlight one other great
adaptive aspect of the platform,

which is that we started with
this two distinct populations.

That I was talking about earlier, the
low N ni h stroke, milder deficits

with a large clot, and then more
kind of distal and medium clots.

in after we, we released sites in both of
these patient populations, if you will.

We found out that there were some
clinical trials that were presented and

published that showed that we might have
to pivot that latter patient population

a little bit because the question may be
answered in a subset of that population

as to EVT not being better or the
device-based treatment not being better.

So we paused that population, went
back to the drawing board a little bit,

collaborated with the trial PIs of the
published trials, and then, came up

with a redesign and it's Now back with
the IRB for approval, to see if we can

reopen a slightly modified, version
of the protocol for that population.

So that is a great adaptive aspect
where if we have external data, we

can look at it and make sure that
the platform adapts to the, existing

science that comes out in parallel.

Scott Berry: So it, the, trial
was designed to identify groups

where we know the answer.

Yes, you should.

No, you should not do
endovascular therapy.

You're learning from other trials.

Done externally answers to those
questions, which then modify our trial.

And, it's so critical that we, Are
able to adapt to that and continue to

evolve the questions based on what's
known and not known within this.

so it's, a huge feature of this that, that
we're able to do this in another setting.

We might have to stop, shut down the
trial, get new funding and all of this so

that that's an incredible feature of it.

Eva Mistry: And that
aspect is critical, right?

When you, in the typical, typical setting,
you would have to the contractual, you

know, binds won't allow modifications
and you might have to go through

another review process and kind of,
you know, reinvent the wheel and that

might put back the field by years,
like you said, Scott, in this setting,

it's, it's, it's much more nimble.

Scott Berry: So how does this
work also, sort of academically,

we have this NIH trial in it.

Um, is, is Eva Mystery the first author
on every result that comes out of step?

How does this, how, how will
publications work in the academic

setting tied to all of this?

Jordan Elm: Yeah.

And that's one thing I think it, it, it's
a little harder, uh, with the platform

because you don't have, um, uh, you
know, the typical structure of having.

The person who brings forth the
idea kind of being the trial lead.

There's a lot of leaders in this
platform, but we wanna make sure that

the people who come forth with the ideas
are the leads for their asset papers,

um, for, for the, the components of the
science that they've, they're leading.

Scott Berry: Um,

Jordan Elm: So there's a lot of
us working in the background.

I would say just kind of
facilitating the process, um, but.

The, the leadership of the papers,
the, the trial author, um, the,

the paper manuscript primary papers
should be, um, the people who

brought forth those, those questions.

Scott Berry: Yeah, the, so it,
it may be that papers just come

out when results are known.

And it may be that one patient that's
contributing to multiple question there,

they contribute and the papers published.

And meanwhile, this is just a,
a, a continual process to this.

I, I've been struck by, um.

How innovative the NIH has been on this,

how forward thinking they've been on this.

You, you mentioned the
OTA funding of this.

I think this is an incredibly,
uh, uh, you know, forward thinking

way for the NIH to do this.

Uh, Eva, I assume that's been your
experience in the whole process of,

of the creation of this, the, the,
the, the working of all of this.

Eva Mistry: I think they have been
incredibly creative and innovative.

In fact, to tell you a little bit
of their history, we started working

on the design of the platform.

I believe, Jordan, you can
correct me, 2018 public,

2019, uh, something like that.

And, uh.

We did try the usual grant submission
pathway first, and as you can imagine,

there are so many components of the
platform that don't kind of fit in

the, it's like a square peg through
a round hole if you try to fit it in.

So it was in fact an IND S'S idea to.

Uh, put out a notice of special
interest for an other transactional

authority mechanism, um, to submit
this first master protocol, plus a

first domain concept to, to make this
platform into a reality at which.

State, we worked closely with you,
Scott, and, and your team, um,

to, to come up with a protocol
and the, the entire design.

And, uh, so I would say they've been
incredibly kind of innovative, forward

thinking, um, including, I should say,
this industry partnership and the avenues

to, to, to move the science forward as
fast and as cost efficiently as we can.

And most ethically from a
clinical standpoint, frankly,

um, as a clinician, myself.

Scott Berry: Yeah, I, I wonder
if you could touch on that part.

So, as, as a statistician, I always
sit on the side of the design and

I, I find these can be incredibly.

Uh, efficient in patients
contributing to multiple questions.

There, there, there're a placebo
for multiple arms and it just seems

like this is so, uh, uh, uh, great.

From that perspective, running a
trial like this at a site, is it, I,

I, are there benefits on that side?

Do you think that from a
clinical site, from your

perspective in, in this platform.

Eva Mistry: Um, I think there are
multiple benefits, um, to being

a sign and step platform trial.

Um.

Being a step site comes with, um,
infrastructure support from the N-I-N-D-S,

um, to we, NIDS recognizes that running
something like this now add the complexity

of enrolling in a hyperacute setting.

Uh, a patient who has.

This first medical contact with
the system, actually their lives

has been turned upside down.

Oftentimes, they can't
consent for themselves.

We have to consent.

Legally authorized representatives,
they're coming as transport from little

hospitals two hours away, and you're
trying to talk to them while their

family members in the transport to talk
about this, this trial that you have.

So it's operationally
extremely challenging to do so.

When IMDS.

Recognize that and, and is providing
infrastructure support to the all

38 sites, uh, that are participating
in the, in the platform trial.

Uh, we have great support in other ways.

We have robust training.

Uh, we have several PIs at least
of the overall step platform trial,

uh, that train sites on various
aspects of operationalizing.

We have something called the study
hotline, which is a 24 7 hotline

that is staffed by study site.

Study, um, uh, multiple PIs, uh, to answer
urgent enrollment, clinical questions and

kind of support the sites in that process.

So, so there's a lot of work,
there's a lot of teamwork, I should

say, uh, that goes on in, in,
in, in doing a trial like this.

But there are definitely benefits.

And then, like you said, these
questions kind of hopefully keep

coming in perpetually providing
the population that the site sees.

Continuous opportunity to
participate in cutting edge research.

And I'll say for our site, you
know, participation in research

is part of our clinical care.

We want every patient to be considered
for, for opportunities for research

unless, and if we, we don't see ourselves
doing appropriate clinical care.

If we don't at least think about that.

Scott Berry: Yeah, and, and I know
Jordan, we're at the early stages of.

Interim analysis, uh, data
management results, publications.

But from your perspective, you
know, the complexity of four

questions simultaneously, adding
new ones in, how has the, the

operational aspects of all of this.

Jordan Elm: Uh, I would say initially
it felt daunting, but it has become

now, I think, easier than what we

Scott Berry: Okay.

Yeah.

Jordan Elm: which is, it's always good.

I think, um, you know, anytime
you're, you're doing something new

for the first time and it's a little
bit of a learning curve, but I, I

think having the framework here.

Of, uh, the consistency across the
whole platform, uh, more uniformity

with processes, um, is only gonna
make things easier moving forward.

So.

Scott Berry: Yeah.

Yeah.

Uh, and, and we, we need to mention that
there's, there's a whole sets of teams

working on this, uh, from the NIH to the
pharma companies, the statisticians, MUSC.

Uh, tremendous work from everybody on this
is, is, has been really amazing to see.

Largely, uh, you know, raising everybody,
working together, raises everybody, uh,

within this setting has been amazing.

And this is a, this is a sentinel
project, I think for the NIH and

setting a, a, a really cool standard
I think in, in other disease areas.

Jordan Elm: Agree.

Completely agree.

Yeah.

Scott Berry: All right.

So we are, we are as we as, as
Eva said, we are 17 or 18 patients

into this, this Odyssey, so
we're not quite in the interim.

But thank you for joining.

In the interim,

Jordan Elm: Thank you.