August 22, 2025 • 43 mins
“If you can drive the brain’s naturally occurring activity, what you can get is the biologic expression that is important for brains to maintain and protect themselves,” Cognito Therapeutics’ CEO Christian Howell tells Bloomberg Intelligence in this episode of the Vanguards of Health Care podcast. Howell sits down with BI analyst Matt Henriksson to discuss the company and its Spectris device — a non-invasive therapeutic intervention designed to use gamma waves to preserve brain structure and function, starting with Alzheimer’s patients. He also highlights the promise of Cognito’s Hope study and reflects on how his time in the Navy and at Medtronic under former CEO Omar Ishrak shaped his “fidelity to the mission” leadership mantra.
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Episode Transcript
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Speaker 1 (00:18):
Welcome to another episode of the Vanguards of Healthcare series.
My name is Matt Hendrickson, the medical technology analyst at
Bloomberg Intelligence, which is the in house equity research platform
of Bloomberg LP. We're pleased to have with us today
Christian Holle, CEO of Cognito Therapeutics, a privately held medical
device company that is innovating to potentially improve the lives
(00:39):
of patients living with neurodegenerative disease. Christian, thank you for
joining us today.
Speaker 2 (00:44):
Matt, thanks so much for having me and.
Speaker 1 (00:46):
Christian, you know, with Alzheimer's and other neuro generate diseases.
But let's start with your path, your career path, and
how you got to be the CEO role of Cognito.
Speaker 2 (00:59):
Yeah.
Speaker 3 (01:00):
You know, I really think about my professional path starting
with my time as an officer in the Navy. It
was incredibly formative for me, and really what it sort
of grounded me was a life of service, was a
focus on being in service to others, and so you know,
when I had the opportunity to finish that time, I
(01:22):
really wanted to find a professional opportunity that was both
gave me the opportunity to do well right and be
ambitious and be entrepreneurial, but also do good. And so
I was then recruited into medical devices and then spent
probably twenty years in medical devices between mostly Coavidian and Medtronic.
(01:45):
And then the last kind of role that I had
within a medical device company was probably the most formative,
which was I had the opportunity to lead value based
healthcare for Medtronic, and Omar Ishrak, who was the CEO
at the time, had this really grand vision of pivoting
Medtronic from a thirty billion dollar company based in volume
(02:06):
to a thirty billion dollar company based in value. And
what we learned was to do that, several things became
very very important. One was establishing very deep partnerships with
health systems, and then the other was really being as
integrated around the data and the evidence so that you
(02:28):
could determine what was appropriate for patients. And so it
was an incredible experience. It gave me the opportunity really
to travel around the world with Omar and various members,
with Jeff Martha, and with Raccoons, who was the chief
science and medical officer, and really learned from them and
(02:49):
see the way that they guided a business. The way
that they put patients first and candidly, the way their
fidelity to the mission I just thought was fascinating. One
time asked Omar, when they were doing the transition between
Jeff and Omar, what advice he was going to give
to Jeff. And I thought he would give this, you know,
sort of oracle like business answer of you know, you
(03:12):
have to focus on this with the investors. But what
he what he said to me was it's about fidelity
to the mission. And when Earl Bakin started Metronic, he
was very clear on mission. And then I thought to myself, Okay, look,
this is really interesting. The Navy was so much about,
you know, the mission of supporting and defending the Constitution
of the United States, and then Omar and Metronic that
(03:36):
team was so much about, you know, being a biomedical
engineering company to alleviatep and restore health extent life. And
so it became very clear to me that mission driven
organizations really are are different. Yeah, and then I had
an opportunity to join I saw at Metronic this importance
around data and evidence and had an opportunity to join
(03:59):
a data real what evidence company that was focused on
taking data and doing really robust analysis against is to
help inform better decisions called ation, and I led their
medical device and diagnostics business in addition to their government
and their commercial payer business. And that was incredibly interesting
because I got to see just how important data was
(04:20):
into making decisions about which intervention should be used and when.
And so one of our clients was Cognito, and so
I was fascinated by the technology, got to know the
leadership team, got to know the CEO at the time,
Brent Vaughan Rick Koontz, who I had worked very closely
with at Metronic, joined the board, and you know, they
(04:42):
reached out and said, well, we really need to think
about how we bring this to market in kind of
an innovative way.
Speaker 2 (04:46):
And so I was hired as the chief commercial officer
in twenty twenty three and then.
Speaker 3 (04:51):
Was asked to step up as CEO in August of
last year. So it's been really a tremendous experience.
Speaker 1 (04:57):
Yeah, and why don't we ground the listeners about Cognito
and the specifically the spectrous device. Yeah, does and just
a kind of quick overview of what the product gives
to the patient.
Speaker 3 (05:09):
Yeah, So we're trying to approach sort of NORDI genetic
diseases and Alzheimer's specifically very differently, and so we're using
a non invasive approach which is really focused on driving
a neuroprotective environment. So we use light and sound therapy
to stimulate the the optic and the auditory nerve which
(05:34):
to a particular frequency at forty hertz, and then at
forty hertz we see the brain drive very specific biology
and we can go into what that biology is.
Speaker 2 (05:46):
But we deliver this on light through a headset.
Speaker 3 (05:48):
Patients wear it for an hour a day every day.
We've had tremendous adherents in our studies to date. But
what it enables is it enables this biology of synaptic
protein generation and myelin and glymphatics function and vasoactivity to
(06:08):
create an environment that helps preserve cognition and functions.
Speaker 1 (06:14):
And from the pictures I've seen of it, it looks
like like a VR headset that the patient wears.
Speaker 2 (06:18):
Right.
Speaker 3 (06:19):
That's exactly right and candidly we designed when we really
understood how the technology and the science would work, and
really just the sort of safe and sort of elegant
nature of how it could be delivered that allowed us
to really do a good bit of UX research into
(06:41):
what would be the right design for an Alzheimer's patient,
and so, you know, it's a very intuitive headset. It's
self guided, so when the patient turns it on, there
are voice prompts to let them know that their sessions
about the beginning gives them key markers of time during
(07:01):
the session. And then all of that data is brought
to the cloud where we're able to see the duration
the patient uses when the patient uses the device. And
then ultimately when we come to market, we are you know,
currently an investigational device going through the FDA process or
planning to. We will then be able to share that
(07:25):
data with the prescribing physician who can look at the
data to help us drive compliance and adoption within the patient.
Speaker 1 (07:34):
Yeah, and then you know, starting with Alzheimer's disease itself,
you you've highlighted gamma waves. What exactly are gamma waves
and kind of how does that play into just the
whole you know, physiological events of a patient that is
unfortunately progressing through the disease.
Speaker 2 (07:52):
Yeah, it's a great question.
Speaker 3 (07:55):
You know, it really helpful to think about sort of
the foundation and the and the genesis of cognito through
this lens, so Cognito was started out of MIT, and
it was two leading neuroscientists that kind of met in
the hallway. The first was doctor leeway Si who was
leading the Peak Hour Institute and had been studying the
(08:15):
various activity levels of the brain and the biology that
occurs at each of those activity levels. And then doctor
Ed Boyden, who had been a pioneer of optogenetics, and
he was exploring what were the different modalities that could
be used to control.
Speaker 2 (08:34):
The activity of the brain.
Speaker 3 (08:36):
And so they came together and said, well, what if
you could find a way to stimulate the brain to
a particular activity level and then therefore modulate the biology
that is corresponds.
Speaker 2 (08:46):
With that activity level.
Speaker 3 (08:47):
And so what we know is that the brain, it
really has five different activity levels throughout the course of
our day. But when we are most active and most
deep in thought, the brain as or neurons fire at
a frequency that we call gamma, which is forty hertz.
Speaker 2 (09:06):
Is measured at forty hertz.
Speaker 3 (09:08):
And so when they looked and said, okay, well what
happens at forty hertz, they found this sort of profound
biologic portfolio which.
Speaker 2 (09:18):
Was we saw in the.
Speaker 3 (09:21):
Spinal fluid cell proteins express that were synaptic proteins and
myelind which meant, oh, we have confidence that this at
forty herts were starting to drive these kind of key
elements to brain health. We saw the glymphatic system turn on,
which is a filtration system of the brain, and then
we saw a vase of activity increase, and that sort
(09:44):
of said, Okay, those are enormously important for brain health
and to protect the brain or fortify the brain against
the progression of neurodrogeneral disease.
Speaker 2 (09:53):
What happens in a.
Speaker 3 (09:56):
Diseased brain, what happens in a brain that has Alzheimer's
And what they found was that the an Alzheimer's brain
is restricted in its ability to reach gamma. Okay, and
it's not that the brain can't reach gamma, but its
ability to do it as frequently or do it.
Speaker 2 (10:14):
It's for its long as duration. It's really suppressed.
Speaker 3 (10:17):
But what's interesting is because we're stimulating the brain for
forty hurts, we're able to hold forty hurts safely for
the hour of therapy. So that's why you get this
sort of profound biologic expression that would be you know,
even more than you would see in that patient in
a in a common day and I'm.
Speaker 1 (10:34):
By jumping too far ahead and saying that it's the
the cessation there, you know, the stopping of the gamma
waves at the forty hertz is what then triggers some
of the other you know, with the synatic genes, with
the myelin genes. You know, is that is it really
(10:54):
does it start when the gamma waves stop going at
forty hertz?
Speaker 4 (10:58):
Or is am I?
Speaker 1 (10:58):
Am I simplifying it?
Speaker 2 (11:00):
Yeah?
Speaker 3 (11:00):
I would think about it this way that there's there's
the pathology of Alzheimer's disease and other neurodegenerat diseases, right,
and we're all we've become very familiar with amyloid plaque,
right in this idea that there are or tau tangles,
there are these sort of proteins or plaques that build
up on the exterior wall of the neuron or within
(11:20):
these tangles that occur within the neuron that are really
that are that are starting to deteriorate or degenerate the brain.
Speaker 2 (11:30):
And so what we think.
Speaker 3 (11:31):
About is what are the waves that you could drive
biology that could protect or fortify the neuron and the
synapses in the face of those you know, those pathologies,
because the other thing that we know is that Alzheimer's
is a polypathological disease. It's not just amyloid INTAEL, it's
(11:51):
amloid INTAEL and vascular to mension, all these other elements
to it. Right, So the idea that you're going to
single target a you know, just amyloid or just how
doesn't take into consideration all these other elements.
Speaker 1 (12:05):
Actually kind of just answered my question that you answered
that next question because I know that you know, you're
talking about amyloids and TAW and that's kind of when
you think of the pharmaceutical approach. They're approaching those proteins,
so it seems like there's more than just those proteins
that need to be addressed.
Speaker 2 (12:20):
That's right, you know.
Speaker 3 (12:20):
I mean at the recent aai C meeting the Alzheimer's
Association and National Conference, I think that there was a
very broad consensus that the advancements of these amyloid targeting
therapies are incredibly important, right, but unfortunately they they are
(12:42):
only able to impact a relatively narrow population of patients
at an earlier stage of the disease, which makes early
stage diagnosis are really important.
Speaker 2 (12:53):
And they come with some particular risks. Right, there's a
risk of.
Speaker 3 (12:58):
Something called ARIA, which is amyloid related imaging abnormalities or
brain hemorrhages or microhmorrhages in the brain, and they can
be quite burdensome to the patient, but they also sort
of just target the you know, amyloid. And so what
I think we found at the AI SEE is this
(13:19):
real acceptance now that this is going to have to
be if it's a polypathologic disease, it's going to have
to be a polymechanistic solution. And so, you know, we
think we're driving a very multi mechanistic approach with the
different biomarkers that we're seeing. But I think what you're
going to find is, like cancer or others, you're going
(13:40):
to find a really a sort of combination approach of therapy.
Some that act as as my son likes to say,
some that act as a shield, and some that act
as a sword. And so I think the amyloid therapies
are going to be very important, but I think we're
also going to have to find ways to promote brain
health threa protect brain health.
Speaker 1 (14:02):
Yeah, and you know, let's let's dive deeper into spectras.
Then you know, we talked about the game away, we
talked about the headset design. What exactly is the proprietary
visual and auditory stimulations that are designed to preserve the
brain structure? How, how does how does that work? And
how does that kind of differentiate you from potentially other
(14:25):
offerings that could have a headset like that.
Speaker 3 (14:27):
Yeah, it's a great question, and it's it's one of
the things that I think, uh, the early leadership of Cognito,
and I really credit that the former you know, the
two CEOs that preceded me in as well as Gerald
Chan who is the chairman of our board, that I
think they guided the company to be very you know,
(14:50):
proactive around the prosecution of intellectual property. And so we
have a very very robust IP portfolio that we not
just in the design of the headset and not just
in the particular disease states, but really broadly on the
stimulation of the brain to a particular frequency level, agnostic
(15:10):
of the approach. And that's important because it goes to
what to Ed and Leeway's research, which was, you know, look,
we know activating the brain to GAMA is incredibly important.
What's the safest and most effective way to do that right,
and we're seeing this idea of brain stimulation and brain
activity becoming much more ubiquitous in the market. We're seeing
(15:33):
transmagnetic and focused ultrasound and alternatelying current. But what we've
learned is that by stimulating the optic and the auditory nerve,
really there's two or three things that are very important
about that. One is it makes it incredibly safe. Two
is it allows you to do it anywhere, so you
can do it in a patient's home or the patient
(15:54):
could take the therapy with them. Three is, because of
where the optic and the auditory nerves turn erminate in
the brain, they drive this global response. And so one
of the things that happens when a patient is prescribed
specters or when a patient will be prescribed spectrs is
the first thing that will happen is they will and
(16:15):
we're doing this in our in our trials that are underway.
A patient will receive a clinical cognitive measure called a MMS,
a mini mental state exam, and there are ranges in
that to help determine the severity of the disease.
Speaker 2 (16:32):
The second thing.
Speaker 3 (16:32):
They will take as a blood test to confirm the
presence of amyloid, and so they call that a p
TAU a PTEL either a one eighty one or two seventeen,
which helps confirm the presence of amyloid from their patients
come into an EEG session and the first thing we
do is we give the patient the headset and we
turn it on to make sure that they can tolerate
(16:54):
the sound and the light. About ninety seven percent of
patients have no issue with it. There are some patients
that have some light sensitivity, and as you get into
more progressed Alzheimer's patients, they are challenged to sit for
an hour. We then turn the device on under an
EG and we confirm that we're able to get the
(17:16):
gamma response. And what's fascinating is when you just see
a auditory stimulation, you see part of the brain begin
to oscillate, and when you turn on just a visual
you see another part of the brain. But when you
turn on both audio and visual, you see almost a
global response. And that global response is what makes the
(17:38):
biologic expression so significant and why we're seeing such a
strong biomarker response and then clinical response and the preservation
of cognition and function.
Speaker 1 (17:50):
Yeah, well it kind of sounds like more than some
of the parts.
Speaker 3 (17:53):
That's right, That's exactly what I think, and for me,
it's helpful to think about it. You know, I think
oftentimes what we think about is targeting. You know, we're
targeting amyloid, or we're targeting a particular substance or element.
What we're really targeting is the brain. And what we're
saying is is that if you can drive the brain's
naturally occurring activity, what you can get is the biologic
(18:18):
expression that is important for brains to maintain and protect themselves.
Now we're able to do it safely for an extended
period of time, which is why we're getting the more
pronounced expression. But this idea of driving multiple mechanisms is
so important and really one of the best ways to
do it is to allow the organ you know, it's
(18:39):
to allow the brain itself to drive those mechanisms.
Speaker 1 (18:42):
Yeah, that kind of goes back what you were saying earlier,
is that the initi that main activity of having the
you know, forty hurt scamma waves naturally doing it. It sounds
like the cognito therapeutics it's helping just jumpstart that.
Speaker 2 (18:53):
That's exactly right. Yeah, that's exactly.
Speaker 1 (18:55):
And you know, you talked about, you know, the testing,
make sure that patients are okay with you mentioned the
ninety seven percent are comfortable with having the headset on
and with the lights and the auditory sensation. But there's
more results from the overture study. Could you just walk
through the with the listeners some of the key clinical
(19:16):
results that you saw from that study.
Speaker 2 (19:18):
Yeah, you know, And I think.
Speaker 3 (19:21):
What I think is so important about this question is
I do think it's one of the places that really
differentiates Cognito, which is the commitment throughout since it's founding
two substantive clinical research. So there is an enormous amount
of pre clinical research that's been generated from MIT and
(19:45):
Harvard and Oxford and others around the impact of forty herts.
Speaker 2 (19:49):
There are over one.
Speaker 3 (19:50):
Hundred and thirty clinical trials ongoing around the use of
forty hertz, not just in Alzheimer's, but in an array
of disease and conditions. And we're incredibly fortunate that all
of those funnel to us. But what Cognito has decided
to do is to say, look, we want to you know,
it's been said that the pre you know, for a
(20:11):
drug therapy. The evidence expectation or the evidentiary is in
the pre market and the evidentiary burden for devices in
the post market. And what's been asked by CMS and
others is to really lean in and do more pre
market evidence generation so that we can see larger studies,
we can see more representative studies, and so that's what
(20:32):
Cognito has really done. So we are currently in our
fifth human study, which is called the Hope Study YEP,
and it has We've just enrolled patients six hundred and
seventy three, which is our last patient in and it
(20:54):
will be a twelve month randomized sham controlled trial which
is conducted at seventy sites across.
Speaker 2 (21:01):
The United States.
Speaker 3 (21:03):
We will have our last patient out of the study
in July of twenty twenty six, and we will deliver
the top line findings in August of twenty twenty six,
and then we can talk a little bit about the
FDA pathway it looks like from there. But what really
led us to that study and why we had so
(21:23):
much confidence in doing a study of that size. Now,
this is the largest non pharmacological study that's ever been
done in not just an AD but in any neurodigenerative condition.
And the reason why we were so confident doing that
is because of overture, and so overture was our pivotal study.
And what we discovered in overture was that it was
(21:45):
a six month study, it was done across seventy four patients.
It was we looked at a series of endpoints because
we were trying to determine what the endpoints that we
should capture in hope we're going to be And what
we found was this profound impact within a seventy seven
(22:06):
percent preservation of function, which is measured in a test
called the ADCs ADL, which is activities a daily living,
a seventy six percent preservation of cognition measured through the MMSC,
and then a sixty nine percent preservation of brain volume.
And why that was so interesting was that what that
(22:27):
tells us is that those those mielin proteins that we're
seeing at sixty days and the MRI results we're seeing
at ninety are the general or then resulting in MRI
at the one hundred and eighty day mark that are
telling us that in a large number of patients we
are preserving the brain volume, but in almost fifty er
(22:51):
sound the patients, we're seeing restoration of myelind So that's
very exciting to think about what we might be seeing
here coming forward in the Hope study. And and so
we we are, you know, we are, we are very
sort of uh committed and focused to driving as as
sort of robust and as organized as study as possible
(23:16):
because we think the results can be could be very
compelling and obviously enormously meaningful to patients.
Speaker 1 (23:22):
Yeah, and just refresh me for a moment, because I'm
only my goggles are specifically on medtech, so I'm not
on the pharmaceutical side. I'm sure there's listeners who are
new to the pharmaceutical spaces as well. But when I'm
thinking of like look can be and I'm thinking of
other anti embloid pharmaceutical options, those don't reverse the progression, right,
they just limit everyone.
Speaker 3 (23:43):
Everyone at this point is talking about the preservation of
cognition and function. That's the measure, right, including us, Right,
we are talking about compared to a cham arm how
much are we able to preserve cognitive funk and general function. Now,
(24:04):
when we look at the results of their studies, they
were in the mid twenties, mid thirties on the preservation
of cognition and functions. So seeing results in the mid
seventies is enormously exciting. But then also the safety is
a major concern. Right there was some pretty significant aria
(24:26):
events and then we've had no device related adverse events
in the course of our study. We've also been very
happy to see the level of adherence, meaning patient's commitment
to the therapy. So you know, oftentimes when we talk
to people and we say, oh, we're going to ask
them to do it an hour day every day, you know,
you can see that there's this sort of quizzical look
that goes on, like that's a lot. What we see
(24:48):
is in overture, we saw eighty five percent of patients
we're doing the device at least six days a week
at least fifty minutes a day, which is incredible. In
the current study because we're able to see the data
from the download, we're at eighty eight percent. And we're
also seeing one of the things that we do after
each study, because it's a sham studies, we do an
(25:10):
open label extension, meaning patients have the ability to if
they were on either arm, they can stay in the
study for an additional period of time, we saw an
eighty three percent migration from the over your study into
the oil and we're seeing almost a mid ninety percent
now in populations that's coming in to theale on hope
(25:34):
because one of the things we're offering in the OLEE
is an open view goggle. So the glasses to this
point have been accluded. Patients haven't been able to see
through them. All they can see it's the light in
the yeah. But as we think, as we think about
what the device will look like ultimately on market, you know,
if and when we receive the FDA approval, it will
(25:56):
be at what we call an open view lens, so
patients will be able to see around them. They would
be able to watch the television. They would they wouldn't
be able to listen to the TV because they need
the sound therapy, but they would be able to do activities.
And we that's been a huge draw for patients. I
think they're very excited about that ability.
Speaker 1 (26:13):
To so I feel like that's a game changer right there.
Speaker 3 (26:16):
I think the you know, one of the things we
hear from patients is and I think it's a really
interesting thing.
Speaker 2 (26:22):
Given our shared background in.
Speaker 3 (26:23):
Medtech, right, and is there's a there's an empowerment that
comes from being giving a device that you know, it's
confirmed that it's able, it's able to evoke gamma. Right,
So the patient knows, Okay, if I wear this thing,
my my brain's going to respond to it. And if
I wear this thing, I understand that the science has
(26:45):
told me that there's going to be a corresponding biology.
Speaker 2 (26:48):
So now I have this thing, I have.
Speaker 3 (26:50):
This this physical object in my home that if I,
you know, integrated into my daily activity, I can be
proactive about my disease. And this is a disease that
has just absolutely victimized people for years. And so this
idea that I'm now empowered to wear something every day
that I know is going to have a positive impact.
(27:12):
I think that's why we're seeing such high levels of
adherents and adoption. And I do think the idea of
bringing a device into this space feels game changing.
Speaker 1 (27:24):
Yeah, no, it's absolutely agree with that. And so now
I'm you know, I'm putting on my analyst's head on
and I'm doing Now I'm starting to do the timeline.
And you've mentioned that the Hope study, the enrollment has
been completed. You mentioned it the twelve month endpoints, so
twelve months from now would be August of twenty twenty six,
(27:44):
give it maybe a few extra months to kind of
gather the data, analyze the data. Maybe potentially you know,
data presentation from the Hope study in end of twenty
six or early twenty twenty seven. Does that lead you
on a path potentially for FDA approval in middle of
twenty twenty seven perhaps, or is it? Let me actually
(28:07):
stop first and say, is it expected to be a
five to ten K approval PMA approval the Novo? And
then how does that then play into that timeline for
my mid twenty twenty seven guests.
Speaker 3 (28:18):
Yeah, it's as if you're in my board meeting, So
let me give you the timeline. So we are a
breakthrough device through the FDA, and we are a Denovo device,
and so and one I really applaud I think there
are different dispositions when CEOs come in talking about FDA
(28:40):
and CMS, and I want to applaud both organizations in
that I think that they've been very proactive in saying, look,
we want to raise the bar on the quality of
evidence that we're seeing from medical device companies because we
appreciate that there are some challenges in you know, mbursement.
(29:00):
We want to see more evidence, and from a regulatory perspective,
we want to see a better demonstration of effectiveness and safety.
But programs like Breakthrough and early Payer Feedback and tap
of allowed companies to get much more aligned with the
FDA and have better understanding of expectations and timelines. So
(29:22):
for us, we think it'll be last patient out in
July twenty six, top line data in August of twenty six.
We would like to submit to the FDA somewhere in
that October November time frame of twenty six. We work
very closely through the sprint process to make sure that
when we submit, we've got good clarity into what the
expectations are of the FDA, and they've answered many of
(29:44):
our questions that would hopefully put us at a marketing
approval from the FDA or authorization in early twenty seven,
first half of twenty seven.
Speaker 2 (29:56):
If you think about.
Speaker 3 (29:57):
A six to nine month review window and then you
know then it, then it becomes interesting because that's where
the world changes for many companies.
Speaker 2 (30:06):
Because drug therapies and.
Speaker 3 (30:08):
Coverage and reimbursement is very different than for uh, for
device therapy.
Speaker 1 (30:14):
Yeah, and let's let's let's talk about that, you know,
the combination of the commercialization versus kind of perhaps the
economics for CMS of a device versus you know, a
pharmaceutical option. First you talked about with the breakthrough device,
so you are you're talking about CMS simultaneously. What is
what's the goal for reimbursement. Is it something where you're
(30:37):
planning to sell the headset to each patient or is
it a monthly rental you know, fee? And then kind
of how does that work then either complementing some of
these anti amyloid medicines or potentially as an alternative option.
Speaker 3 (30:54):
Yeah, and I think in this space it's a lot
of to be determined, But I'll give you what I
think are kind of aspiration is or what our plan is, right,
which is one is there is a program that has
been put forward by CMS n FDA which is called
Transitional Coverage for Emerging Technology. So there has been in
(31:14):
probably the last four presidential administrations kind of a back
and forth about how they think about the reimbursement of
breakthrough technologies, and the Trump administration and the current leadership
at FDA has been very i think outspoken, very public
that they believe that the work should be done to
(31:39):
enable concurrent coverage decisions with a regulatory decision. So our
intention at this point is to certainly apply for that program.
That program is limited the number of spots it takes
per year, per cycle, but one of the things they
are looking at is the impact and the patient population
(32:00):
and the prevalence or lack thereof of therapies in that space.
And we know for the vast, vast majority of Alzheimer's
patients there is just not any type of therapy available
to them. So that sort of let's call that sort
of path a and then you get the opportunity to
work very closely with CMS provide the necessary evidence around
(32:21):
how it should be coded its benefit category. I think
the benefit category would be that of durable medical equipment
MEAN and so the payment model on that can shift,
but traditionally it's either pay at the time or pay
over a year or thirty.
Speaker 1 (32:37):
Yeah, thirty yeah, I'm thinking of like the diabetes companies.
Speaker 3 (32:40):
Yes, right, And so that the unit's a pretty well
established and we've heard from in our market research, we've
heard from from payers from commercial payers that you know,
chronic therapies for chronic conditions is very tough. So think
about the glps. I'm struggling with the disease. The GLP
can resolve the disease, but I have to continue to
pay for the GAIL and when I don't, the disease returns.
(33:02):
Versus I have a chronic disease like Alzheimer's disease. I
pay for a therapy once and then it's durable for
three to five years, and then really what we're talking
about is driving adherence that the patient continues.
Speaker 2 (33:15):
To utilize the therapy.
Speaker 3 (33:17):
So that would be I think the benefit category there
is what they call the hick picks or the coding process.
You have to determine whether there's an existing code for
what you're doing. Given how the the iniquity of what
we're talking about with is an at home therapy for
Alzheimer's disease, there's obviously not an existing code, so that's
(33:38):
something that we would explore. And then really it's creating
the evidence necessary and CMS was very clear that they said, look,
we have some expectations from medtech companies that one you
do more robust evidence generation in the pre market. Two
that you do it representative of the population and looks
(33:59):
you look an impact, three, that you make it diverse,
and that four that you are thinking about engaging us early.
And we really feel well positioned in that right. We're
the largest study that's ever done in this space, and
being our fifth study, we are obviously very representative of
medicare population because that's what we've included in all of
(34:20):
our studies is the is the age group of Alzheimer's.
We are extremely diverse in our study and what we
enrolled in that in the study, and then we've we've
tried to engage as early as possible. But it's it's
something that we're really going to have to think about
because there's going to have to be a balance between
(34:41):
making sure that we find a way to get this
to the patients that need it, and then we but
that we you know, we price it and we cover
it accordingly. You asked a question about, you know, in
combination that I do think is one of the things
that's so interesting about the safe of the device is
(35:03):
and the and the and the mechanism being as novel
as it is, that I do think it does align
itself for use in advance of other drug therapies, use
in combination of other drug therapies or other therapies, and
use post of those therapies. So it'll all need to
be studied and explored and applied to you know, submitted
(35:25):
to the regulators. But the pre clinical evidence tells us
that there's nothing that would stand in the way of
that being an option.
Speaker 1 (35:34):
Yeah, And it's interesting that you talk about being used
in advance of the pharmaceutical options, and it's in my mind,
I'm theoretically thinking that you could potentially scan for these
patients earlier in the progression. And it almost comes to
a point where could it be where theoretically you could
be scanned for gamma way of activity and basically if
(35:59):
you're seeing in the game away activity go below the
forty hertz, you go on to the therapy or is
that too ston to like think?
Speaker 3 (36:06):
No, I think, well, I think it'll be thought about
a little bit differently, but I think it's I think
it's a really good point, I think, which is one
we are obviously seeing an explosion in the early stage diagnosis.
Speaker 2 (36:17):
Of Alzheimer's disease.
Speaker 3 (36:18):
It's both the encouragement and the education of that from
the lilies and the biogens in the East sides of
the world that are saying, well, our therapies are most
impactful in those patients earlier in their disease progression, and
it's important. Right, there are seven million people in the
United States with Alzheimer's disease.
Speaker 4 (36:35):
Right.
Speaker 3 (36:35):
There are twelve million people with mild cognitive impairment, which
is the earliest stage, ten million of which are undiagnosed. Yeah,
so that's staggering. So one, we've seen new approvals in
biomarkers and diagnostics that is going to make it much
easier to get those patients diagnosed. But I think what
(36:57):
you're going to see is you're going to see real
challenge in two parts. I talked to a leading neurologist
last week at the ai CE and she told me
that she had screened thirty five hundred patients for the
amyloid therapies and four hundred were able to progress to treatment.
That's thirty one hundred patients that are left without a solution. Yeah,
(37:19):
that's an enormous number of patients that are now diagnosed
and looking around saying, well, that's what can I do?
Speaker 1 (37:26):
Well, Actually, I'm just now curious what's the main exclusion factor.
Speaker 3 (37:31):
It can be the risk to the side effects. It
can be the different you know, sort of genetic testing
that occurs. It can be the stage of the disease.
It can be it can be an array of things
that disqualifies them from the amyloid targeting therapies. It can
be other comorbidities or conditions, and so that so one
(37:54):
you have this bolus of patients, you know, these folks
that are in desperate need of it, So to see
more and more patients diagnosed earlier, you're going to see
them go through which is going to increase the burden
to the neurology practices, which they are already at capacity
and struggling. You're going to see of a limited number
(38:17):
get approved. And then lastly, I think what you'll see
to your question is technologies like Spectrius would have the
opportunity to really mobilize the.
Speaker 2 (38:28):
General practitioners and the geriatricians.
Speaker 3 (38:30):
Because what they could say is, Okay, I'm going to
give an MMSC and a blood test. I'm going to
flag that this patient is at risk for or has
Alzheimer's disease. I'm going to immediately get them on spectris
to start preserving cognition and function. And then if we
decide to put them into a care pathway that explores
(38:52):
the amiloid target therapy, great, but that process can take
a long time. So this is an opportunity to be
as early and proactive as possible in getting patients of therapy.
Speaker 1 (39:02):
It sounds like you have quite a busy year eighteen months,
twenty four months, But I'm going to just go even
what else is there? Because you know you are doing
some other pre clinical work and so you know, between
you know, the early clinical work for parkinson disease and
other developments, how do you see the state of neuroscience
(39:24):
in five to ten years and how does cognitive fit
into that?
Speaker 2 (39:27):
I don't.
Speaker 3 (39:28):
This is where you're going to hear real excitement in
my voice because one, you know, as we've talked about
the kind of mechanism of action, what you didn't hear
me say was anything that was specific to Alzheimer's.
Speaker 2 (39:39):
Our story doesn't begin with Alzheimer's's kind of.
Speaker 3 (39:41):
Ends with it, right, which is we believe that we
can drive this biology, which it creates a neuroprotective environment
that we think is very important with those with neurodegenerator
disease and where we're first exploring testing that is in
ad patients, but we believe that there's an opportunity for
that to be impactful in as you mentioned, other degenerator
conditions and PD and MS and Louis body and a
(40:07):
whole other area of nirogenetics. We believe it's potentially impactful
in brain injury like stroke and traumatic brain and concussion.
We believe it's potentially impactful in areas like addiction or
mood disorders or sleep. But we believe that because we
(40:27):
have this incredible flywheel of evidence coming from the preclinical
what we've really started to do is to create what
we're calling brain health collaboratories, which are you know, let's
think about what we have sort of unique to us.
One is we have this incredibly safe, potentially enormously impactful technology.
(40:52):
We have a tremendous amount of preclinical signal coming from
leading academic centers around the world, and we think we're
going to have this various of broad application to it.
So what we want to make sure we're doing is
that we're exploring those in real partnership with leading academic
centers around the United States. So we're going to be announcing.
Speaker 2 (41:11):
Our first collaboratory with the.
Speaker 3 (41:14):
Rockefeller Neuroscience Institute at West Virginia University Medicine that I'll
be coming in the next couple of weeks. But what
that will allow us to do is to not only
do the evidence and research necessary to prepare for an
Alzheimer's launch, to not only think about how we should
explore more broadly in Alzheimer's disease specifically, but then how
(41:35):
should we explore research in these other areas that we
think we've got pre clinical signal for. So I think
it's got an opportunity to truly reshape neuroscience. And I
think we're going to see in neuroscience is like or
in what we've seen in others. Right, medical technologies completely
disrupted cardiology with ablation of racil fibrillation and implannable cardiac devices.
(42:02):
We saw medical technologies non pharmacological, completely disrupt oncology with
radiation therapy and break your therapy, and technologies like novercure.
We've seen it early stage in neurology with deep brain
stimulation and TMS and others. And I think what this
is going to show is in these neurodegenerative conditions. Here's
(42:22):
an opportunity to not only use a non pharmacological, but
a non invasive at home therapy for that, which I
think is unbelievably exciting.
Speaker 1 (42:32):
Yeah, and I tell you what, Chrishan, I'm looking forward
to having you back on again to dive deeper into
those fields. But thank you so much for joining us today.
It was a great conversation.
Speaker 2 (42:41):
Yeah, I so much appreciate the time and the engagement.
Thank you so much.
Speaker 1 (42:44):
Yes, and thank you to our listeners for tuning in today,
and we hope you join us for future episodes. If
you'd like to stay up to date, you can click
the subscribe button on Spotify or your favorite streaming platform.
Speaker 4 (42:54):
Take caress.
Speaker 2 (43:17):
Uses, musings, nomos
Speaker 4 (43:25):
Uses,
Welcome to another episode of the Vanguards of Healthcare series.
My name is Matt Hendrickson, the medical technology analyst at
Bloomberg Intelligence, which is the in house equity research platform
of Bloomberg LP. We're pleased to have with us today
Christian Holle, CEO of Cognito Therapeutics, a privately held medical
device company that is innovating to potentially improve the lives
(00:39):
of patients living with neurodegenerative disease. Christian, thank you for
joining us today.
Speaker 2 (00:44):
Matt, thanks so much for having me and.
Speaker 1 (00:46):
Christian, you know, with Alzheimer's and other neuro generate diseases.
But let's start with your path, your career path, and
how you got to be the CEO role of Cognito.
Speaker 2 (00:59):
Yeah.
Speaker 3 (01:00):
You know, I really think about my professional path starting
with my time as an officer in the Navy. It
was incredibly formative for me, and really what it sort
of grounded me was a life of service, was a
focus on being in service to others, and so you know,
when I had the opportunity to finish that time, I
(01:22):
really wanted to find a professional opportunity that was both
gave me the opportunity to do well right and be
ambitious and be entrepreneurial, but also do good. And so
I was then recruited into medical devices and then spent
probably twenty years in medical devices between mostly Coavidian and Medtronic.
(01:45):
And then the last kind of role that I had
within a medical device company was probably the most formative,
which was I had the opportunity to lead value based
healthcare for Medtronic, and Omar Ishrak, who was the CEO
at the time, had this really grand vision of pivoting
Medtronic from a thirty billion dollar company based in volume
(02:06):
to a thirty billion dollar company based in value. And
what we learned was to do that, several things became
very very important. One was establishing very deep partnerships with
health systems, and then the other was really being as
integrated around the data and the evidence so that you
(02:28):
could determine what was appropriate for patients. And so it
was an incredible experience. It gave me the opportunity really
to travel around the world with Omar and various members,
with Jeff Martha, and with Raccoons, who was the chief
science and medical officer, and really learned from them and
(02:49):
see the way that they guided a business. The way
that they put patients first and candidly, the way their
fidelity to the mission I just thought was fascinating. One
time asked Omar, when they were doing the transition between
Jeff and Omar, what advice he was going to give
to Jeff. And I thought he would give this, you know,
sort of oracle like business answer of you know, you
(03:12):
have to focus on this with the investors. But what
he what he said to me was it's about fidelity
to the mission. And when Earl Bakin started Metronic, he
was very clear on mission. And then I thought to myself, Okay, look,
this is really interesting. The Navy was so much about,
you know, the mission of supporting and defending the Constitution
of the United States, and then Omar and Metronic that
(03:36):
team was so much about, you know, being a biomedical
engineering company to alleviatep and restore health extent life. And
so it became very clear to me that mission driven
organizations really are are different. Yeah, and then I had
an opportunity to join I saw at Metronic this importance
around data and evidence and had an opportunity to join
(03:59):
a data real what evidence company that was focused on
taking data and doing really robust analysis against is to
help inform better decisions called ation, and I led their
medical device and diagnostics business in addition to their government
and their commercial payer business. And that was incredibly interesting
because I got to see just how important data was
(04:20):
into making decisions about which intervention should be used and when.
And so one of our clients was Cognito, and so
I was fascinated by the technology, got to know the
leadership team, got to know the CEO at the time,
Brent Vaughan Rick Koontz, who I had worked very closely
with at Metronic, joined the board, and you know, they
(04:42):
reached out and said, well, we really need to think
about how we bring this to market in kind of
an innovative way.
Speaker 2 (04:46):
And so I was hired as the chief commercial officer
in twenty twenty three and then.
Speaker 3 (04:51):
Was asked to step up as CEO in August of
last year. So it's been really a tremendous experience.
Speaker 1 (04:57):
Yeah, and why don't we ground the listeners about Cognito
and the specifically the spectrous device. Yeah, does and just
a kind of quick overview of what the product gives
to the patient.
Speaker 3 (05:09):
Yeah, So we're trying to approach sort of NORDI genetic
diseases and Alzheimer's specifically very differently, and so we're using
a non invasive approach which is really focused on driving
a neuroprotective environment. So we use light and sound therapy
to stimulate the the optic and the auditory nerve which
(05:34):
to a particular frequency at forty hertz, and then at
forty hertz we see the brain drive very specific biology
and we can go into what that biology is.
Speaker 2 (05:46):
But we deliver this on light through a headset.
Speaker 3 (05:48):
Patients wear it for an hour a day every day.
We've had tremendous adherents in our studies to date. But
what it enables is it enables this biology of synaptic
protein generation and myelin and glymphatics function and vasoactivity to
(06:08):
create an environment that helps preserve cognition and functions.
Speaker 1 (06:14):
And from the pictures I've seen of it, it looks
like like a VR headset that the patient wears.
Speaker 2 (06:18):
Right.
Speaker 3 (06:19):
That's exactly right and candidly we designed when we really
understood how the technology and the science would work, and
really just the sort of safe and sort of elegant
nature of how it could be delivered that allowed us
to really do a good bit of UX research into
(06:41):
what would be the right design for an Alzheimer's patient,
and so, you know, it's a very intuitive headset. It's
self guided, so when the patient turns it on, there
are voice prompts to let them know that their sessions
about the beginning gives them key markers of time during
(07:01):
the session. And then all of that data is brought
to the cloud where we're able to see the duration
the patient uses when the patient uses the device. And
then ultimately when we come to market, we are you know,
currently an investigational device going through the FDA process or
planning to. We will then be able to share that
(07:25):
data with the prescribing physician who can look at the
data to help us drive compliance and adoption within the patient.
Speaker 1 (07:34):
Yeah, and then you know, starting with Alzheimer's disease itself,
you you've highlighted gamma waves. What exactly are gamma waves
and kind of how does that play into just the
whole you know, physiological events of a patient that is
unfortunately progressing through the disease.
Speaker 2 (07:52):
Yeah, it's a great question.
Speaker 3 (07:55):
You know, it really helpful to think about sort of
the foundation and the and the genesis of cognito through
this lens, so Cognito was started out of MIT, and
it was two leading neuroscientists that kind of met in
the hallway. The first was doctor leeway Si who was
leading the Peak Hour Institute and had been studying the
(08:15):
various activity levels of the brain and the biology that
occurs at each of those activity levels. And then doctor
Ed Boyden, who had been a pioneer of optogenetics, and
he was exploring what were the different modalities that could
be used to control.
Speaker 2 (08:34):
The activity of the brain.
Speaker 3 (08:36):
And so they came together and said, well, what if
you could find a way to stimulate the brain to
a particular activity level and then therefore modulate the biology
that is corresponds.
Speaker 2 (08:46):
With that activity level.
Speaker 3 (08:47):
And so what we know is that the brain, it
really has five different activity levels throughout the course of
our day. But when we are most active and most
deep in thought, the brain as or neurons fire at
a frequency that we call gamma, which is forty hertz.
Speaker 2 (09:06):
Is measured at forty hertz.
Speaker 3 (09:08):
And so when they looked and said, okay, well what
happens at forty hertz, they found this sort of profound
biologic portfolio which.
Speaker 2 (09:18):
Was we saw in the.
Speaker 3 (09:21):
Spinal fluid cell proteins express that were synaptic proteins and
myelind which meant, oh, we have confidence that this at
forty herts were starting to drive these kind of key
elements to brain health. We saw the glymphatic system turn on,
which is a filtration system of the brain, and then
we saw a vase of activity increase, and that sort
(09:44):
of said, Okay, those are enormously important for brain health
and to protect the brain or fortify the brain against
the progression of neurodrogeneral disease.
Speaker 2 (09:53):
What happens in a.
Speaker 3 (09:56):
Diseased brain, what happens in a brain that has Alzheimer's
And what they found was that the an Alzheimer's brain
is restricted in its ability to reach gamma. Okay, and
it's not that the brain can't reach gamma, but its
ability to do it as frequently or do it.
Speaker 2 (10:14):
It's for its long as duration. It's really suppressed.
Speaker 3 (10:17):
But what's interesting is because we're stimulating the brain for
forty hurts, we're able to hold forty hurts safely for
the hour of therapy. So that's why you get this
sort of profound biologic expression that would be you know,
even more than you would see in that patient in
a in a common day and I'm.
Speaker 1 (10:34):
By jumping too far ahead and saying that it's the
the cessation there, you know, the stopping of the gamma
waves at the forty hertz is what then triggers some
of the other you know, with the synatic genes, with
the myelin genes. You know, is that is it really
(10:54):
does it start when the gamma waves stop going at
forty hertz?
Speaker 4 (10:58):
Or is am I?
Speaker 1 (10:58):
Am I simplifying it?
Speaker 2 (11:00):
Yeah?
Speaker 3 (11:00):
I would think about it this way that there's there's
the pathology of Alzheimer's disease and other neurodegenerat diseases, right,
and we're all we've become very familiar with amyloid plaque,
right in this idea that there are or tau tangles,
there are these sort of proteins or plaques that build
up on the exterior wall of the neuron or within
(11:20):
these tangles that occur within the neuron that are really
that are that are starting to deteriorate or degenerate the brain.
Speaker 2 (11:30):
And so what we think.
Speaker 3 (11:31):
About is what are the waves that you could drive
biology that could protect or fortify the neuron and the
synapses in the face of those you know, those pathologies,
because the other thing that we know is that Alzheimer's
is a polypathological disease. It's not just amyloid INTAEL, it's
(11:51):
amloid INTAEL and vascular to mension, all these other elements
to it. Right, So the idea that you're going to
single target a you know, just amyloid or just how
doesn't take into consideration all these other elements.
Speaker 1 (12:05):
Actually kind of just answered my question that you answered
that next question because I know that you know, you're
talking about amyloids and TAW and that's kind of when
you think of the pharmaceutical approach. They're approaching those proteins,
so it seems like there's more than just those proteins
that need to be addressed.
Speaker 2 (12:20):
That's right, you know.
Speaker 3 (12:20):
I mean at the recent aai C meeting the Alzheimer's
Association and National Conference, I think that there was a
very broad consensus that the advancements of these amyloid targeting
therapies are incredibly important, right, but unfortunately they they are
(12:42):
only able to impact a relatively narrow population of patients
at an earlier stage of the disease, which makes early
stage diagnosis are really important.
Speaker 2 (12:53):
And they come with some particular risks. Right, there's a
risk of.
Speaker 3 (12:58):
Something called ARIA, which is amyloid related imaging abnormalities or
brain hemorrhages or microhmorrhages in the brain, and they can
be quite burdensome to the patient, but they also sort
of just target the you know, amyloid. And so what
I think we found at the AI SEE is this
(13:19):
real acceptance now that this is going to have to
be if it's a polypathologic disease, it's going to have
to be a polymechanistic solution. And so, you know, we
think we're driving a very multi mechanistic approach with the
different biomarkers that we're seeing. But I think what you're
going to find is, like cancer or others, you're going
(13:40):
to find a really a sort of combination approach of therapy.
Some that act as as my son likes to say,
some that act as a shield, and some that act
as a sword. And so I think the amyloid therapies
are going to be very important, but I think we're
also going to have to find ways to promote brain
health threa protect brain health.
Speaker 1 (14:02):
Yeah, and you know, let's let's dive deeper into spectras.
Then you know, we talked about the game away, we
talked about the headset design. What exactly is the proprietary
visual and auditory stimulations that are designed to preserve the
brain structure? How, how does how does that work? And
how does that kind of differentiate you from potentially other
(14:25):
offerings that could have a headset like that.
Speaker 3 (14:27):
Yeah, it's a great question, and it's it's one of
the things that I think, uh, the early leadership of Cognito,
and I really credit that the former you know, the
two CEOs that preceded me in as well as Gerald
Chan who is the chairman of our board, that I
think they guided the company to be very you know,
(14:50):
proactive around the prosecution of intellectual property. And so we
have a very very robust IP portfolio that we not
just in the design of the headset and not just
in the particular disease states, but really broadly on the
stimulation of the brain to a particular frequency level, agnostic
(15:10):
of the approach. And that's important because it goes to
what to Ed and Leeway's research, which was, you know, look,
we know activating the brain to GAMA is incredibly important.
What's the safest and most effective way to do that right,
and we're seeing this idea of brain stimulation and brain
activity becoming much more ubiquitous in the market. We're seeing
(15:33):
transmagnetic and focused ultrasound and alternatelying current. But what we've
learned is that by stimulating the optic and the auditory nerve,
really there's two or three things that are very important
about that. One is it makes it incredibly safe. Two
is it allows you to do it anywhere, so you
can do it in a patient's home or the patient
(15:54):
could take the therapy with them. Three is, because of
where the optic and the auditory nerves turn erminate in
the brain, they drive this global response. And so one
of the things that happens when a patient is prescribed
specters or when a patient will be prescribed spectrs is
the first thing that will happen is they will and
(16:15):
we're doing this in our in our trials that are underway.
A patient will receive a clinical cognitive measure called a MMS,
a mini mental state exam, and there are ranges in
that to help determine the severity of the disease.
Speaker 2 (16:32):
The second thing.
Speaker 3 (16:32):
They will take as a blood test to confirm the
presence of amyloid, and so they call that a p
TAU a PTEL either a one eighty one or two seventeen,
which helps confirm the presence of amyloid from their patients
come into an EEG session and the first thing we
do is we give the patient the headset and we
turn it on to make sure that they can tolerate
(16:54):
the sound and the light. About ninety seven percent of
patients have no issue with it. There are some patients
that have some light sensitivity, and as you get into
more progressed Alzheimer's patients, they are challenged to sit for
an hour. We then turn the device on under an
EG and we confirm that we're able to get the
(17:16):
gamma response. And what's fascinating is when you just see
a auditory stimulation, you see part of the brain begin
to oscillate, and when you turn on just a visual
you see another part of the brain. But when you
turn on both audio and visual, you see almost a
global response. And that global response is what makes the
(17:38):
biologic expression so significant and why we're seeing such a
strong biomarker response and then clinical response and the preservation
of cognition and function.
Speaker 1 (17:50):
Yeah, well it kind of sounds like more than some
of the parts.
Speaker 3 (17:53):
That's right, That's exactly what I think, and for me,
it's helpful to think about it. You know, I think
oftentimes what we think about is targeting. You know, we're
targeting amyloid, or we're targeting a particular substance or element.
What we're really targeting is the brain. And what we're
saying is is that if you can drive the brain's
naturally occurring activity, what you can get is the biologic
(18:18):
expression that is important for brains to maintain and protect themselves.
Now we're able to do it safely for an extended
period of time, which is why we're getting the more
pronounced expression. But this idea of driving multiple mechanisms is
so important and really one of the best ways to
do it is to allow the organ you know, it's
(18:39):
to allow the brain itself to drive those mechanisms.
Speaker 1 (18:42):
Yeah, that kind of goes back what you were saying earlier,
is that the initi that main activity of having the
you know, forty hurt scamma waves naturally doing it. It sounds
like the cognito therapeutics it's helping just jumpstart that.
Speaker 2 (18:53):
That's exactly right. Yeah, that's exactly.
Speaker 1 (18:55):
And you know, you talked about, you know, the testing,
make sure that patients are okay with you mentioned the
ninety seven percent are comfortable with having the headset on
and with the lights and the auditory sensation. But there's
more results from the overture study. Could you just walk
through the with the listeners some of the key clinical
(19:16):
results that you saw from that study.
Speaker 2 (19:18):
Yeah, you know, And I think.
Speaker 3 (19:21):
What I think is so important about this question is
I do think it's one of the places that really
differentiates Cognito, which is the commitment throughout since it's founding
two substantive clinical research. So there is an enormous amount
of pre clinical research that's been generated from MIT and
(19:45):
Harvard and Oxford and others around the impact of forty herts.
Speaker 2 (19:49):
There are over one.
Speaker 3 (19:50):
Hundred and thirty clinical trials ongoing around the use of
forty hertz, not just in Alzheimer's, but in an array
of disease and conditions. And we're incredibly fortunate that all
of those funnel to us. But what Cognito has decided
to do is to say, look, we want to you know,
it's been said that the pre you know, for a
(20:11):
drug therapy. The evidence expectation or the evidentiary is in
the pre market and the evidentiary burden for devices in
the post market. And what's been asked by CMS and
others is to really lean in and do more pre
market evidence generation so that we can see larger studies,
we can see more representative studies, and so that's what
(20:32):
Cognito has really done. So we are currently in our
fifth human study, which is called the Hope Study YEP,
and it has We've just enrolled patients six hundred and
seventy three, which is our last patient in and it
(20:54):
will be a twelve month randomized sham controlled trial which
is conducted at seventy sites across.
Speaker 2 (21:01):
The United States.
Speaker 3 (21:03):
We will have our last patient out of the study
in July of twenty twenty six, and we will deliver
the top line findings in August of twenty twenty six,
and then we can talk a little bit about the
FDA pathway it looks like from there. But what really
led us to that study and why we had so
(21:23):
much confidence in doing a study of that size. Now,
this is the largest non pharmacological study that's ever been
done in not just an AD but in any neurodigenerative condition.
And the reason why we were so confident doing that
is because of overture, and so overture was our pivotal study.
And what we discovered in overture was that it was
(21:45):
a six month study, it was done across seventy four patients.
It was we looked at a series of endpoints because
we were trying to determine what the endpoints that we
should capture in hope we're going to be And what
we found was this profound impact within a seventy seven
(22:06):
percent preservation of function, which is measured in a test
called the ADCs ADL, which is activities a daily living,
a seventy six percent preservation of cognition measured through the MMSC,
and then a sixty nine percent preservation of brain volume.
And why that was so interesting was that what that
(22:27):
tells us is that those those mielin proteins that we're
seeing at sixty days and the MRI results we're seeing
at ninety are the general or then resulting in MRI
at the one hundred and eighty day mark that are
telling us that in a large number of patients we
are preserving the brain volume, but in almost fifty er
(22:51):
sound the patients, we're seeing restoration of myelind So that's
very exciting to think about what we might be seeing
here coming forward in the Hope study. And and so
we we are, you know, we are, we are very
sort of uh committed and focused to driving as as
sort of robust and as organized as study as possible
(23:16):
because we think the results can be could be very
compelling and obviously enormously meaningful to patients.
Speaker 1 (23:22):
Yeah, and just refresh me for a moment, because I'm
only my goggles are specifically on medtech, so I'm not
on the pharmaceutical side. I'm sure there's listeners who are
new to the pharmaceutical spaces as well. But when I'm
thinking of like look can be and I'm thinking of
other anti embloid pharmaceutical options, those don't reverse the progression, right,
they just limit everyone.
Speaker 3 (23:43):
Everyone at this point is talking about the preservation of
cognition and function. That's the measure, right, including us, Right,
we are talking about compared to a cham arm how
much are we able to preserve cognitive funk and general function. Now,
(24:04):
when we look at the results of their studies, they
were in the mid twenties, mid thirties on the preservation
of cognition and functions. So seeing results in the mid
seventies is enormously exciting. But then also the safety is
a major concern. Right there was some pretty significant aria
(24:26):
events and then we've had no device related adverse events
in the course of our study. We've also been very
happy to see the level of adherence, meaning patient's commitment
to the therapy. So you know, oftentimes when we talk
to people and we say, oh, we're going to ask
them to do it an hour day every day, you know,
you can see that there's this sort of quizzical look
that goes on, like that's a lot. What we see
(24:48):
is in overture, we saw eighty five percent of patients
we're doing the device at least six days a week
at least fifty minutes a day, which is incredible. In
the current study because we're able to see the data
from the download, we're at eighty eight percent. And we're
also seeing one of the things that we do after
each study, because it's a sham studies, we do an
(25:10):
open label extension, meaning patients have the ability to if
they were on either arm, they can stay in the
study for an additional period of time, we saw an
eighty three percent migration from the over your study into
the oil and we're seeing almost a mid ninety percent
now in populations that's coming in to theale on hope
(25:34):
because one of the things we're offering in the OLEE
is an open view goggle. So the glasses to this
point have been accluded. Patients haven't been able to see
through them. All they can see it's the light in
the yeah. But as we think, as we think about
what the device will look like ultimately on market, you know,
if and when we receive the FDA approval, it will
(25:56):
be at what we call an open view lens, so
patients will be able to see around them. They would
be able to watch the television. They would they wouldn't
be able to listen to the TV because they need
the sound therapy, but they would be able to do activities.
And we that's been a huge draw for patients. I
think they're very excited about that ability.
Speaker 1 (26:13):
To so I feel like that's a game changer right there.
Speaker 3 (26:16):
I think the you know, one of the things we
hear from patients is and I think it's a really
interesting thing.
Speaker 2 (26:22):
Given our shared background in.
Speaker 3 (26:23):
Medtech, right, and is there's a there's an empowerment that
comes from being giving a device that you know, it's
confirmed that it's able, it's able to evoke gamma. Right,
So the patient knows, Okay, if I wear this thing,
my my brain's going to respond to it. And if
I wear this thing, I understand that the science has
(26:45):
told me that there's going to be a corresponding biology.
Speaker 2 (26:48):
So now I have this thing, I have.
Speaker 3 (26:50):
This this physical object in my home that if I,
you know, integrated into my daily activity, I can be
proactive about my disease. And this is a disease that
has just absolutely victimized people for years. And so this
idea that I'm now empowered to wear something every day
that I know is going to have a positive impact.
(27:12):
I think that's why we're seeing such high levels of
adherents and adoption. And I do think the idea of
bringing a device into this space feels game changing.
Speaker 1 (27:24):
Yeah, no, it's absolutely agree with that. And so now
I'm you know, I'm putting on my analyst's head on
and I'm doing Now I'm starting to do the timeline.
And you've mentioned that the Hope study, the enrollment has
been completed. You mentioned it the twelve month endpoints, so
twelve months from now would be August of twenty twenty six,
(27:44):
give it maybe a few extra months to kind of
gather the data, analyze the data. Maybe potentially you know,
data presentation from the Hope study in end of twenty
six or early twenty twenty seven. Does that lead you
on a path potentially for FDA approval in middle of
twenty twenty seven perhaps, or is it? Let me actually
(28:07):
stop first and say, is it expected to be a
five to ten K approval PMA approval the Novo? And
then how does that then play into that timeline for
my mid twenty twenty seven guests.
Speaker 3 (28:18):
Yeah, it's as if you're in my board meeting, So
let me give you the timeline. So we are a
breakthrough device through the FDA, and we are a Denovo device,
and so and one I really applaud I think there
are different dispositions when CEOs come in talking about FDA
(28:40):
and CMS, and I want to applaud both organizations in
that I think that they've been very proactive in saying, look,
we want to raise the bar on the quality of
evidence that we're seeing from medical device companies because we
appreciate that there are some challenges in you know, mbursement.
(29:00):
We want to see more evidence, and from a regulatory perspective,
we want to see a better demonstration of effectiveness and safety.
But programs like Breakthrough and early Payer Feedback and tap
of allowed companies to get much more aligned with the
FDA and have better understanding of expectations and timelines. So
(29:22):
for us, we think it'll be last patient out in
July twenty six, top line data in August of twenty six.
We would like to submit to the FDA somewhere in
that October November time frame of twenty six. We work
very closely through the sprint process to make sure that
when we submit, we've got good clarity into what the
expectations are of the FDA, and they've answered many of
(29:44):
our questions that would hopefully put us at a marketing
approval from the FDA or authorization in early twenty seven,
first half of twenty seven.
Speaker 2 (29:56):
If you think about.
Speaker 3 (29:57):
A six to nine month review window and then you
know then it, then it becomes interesting because that's where
the world changes for many companies.
Speaker 2 (30:06):
Because drug therapies and.
Speaker 3 (30:08):
Coverage and reimbursement is very different than for uh, for
device therapy.
Speaker 1 (30:14):
Yeah, and let's let's let's talk about that, you know,
the combination of the commercialization versus kind of perhaps the
economics for CMS of a device versus you know, a
pharmaceutical option. First you talked about with the breakthrough device,
so you are you're talking about CMS simultaneously. What is
what's the goal for reimbursement. Is it something where you're
(30:37):
planning to sell the headset to each patient or is
it a monthly rental you know, fee? And then kind
of how does that work then either complementing some of
these anti amyloid medicines or potentially as an alternative option.
Speaker 3 (30:54):
Yeah, and I think in this space it's a lot
of to be determined, But I'll give you what I
think are kind of aspiration is or what our plan is, right,
which is one is there is a program that has
been put forward by CMS n FDA which is called
Transitional Coverage for Emerging Technology. So there has been in
(31:14):
probably the last four presidential administrations kind of a back
and forth about how they think about the reimbursement of
breakthrough technologies, and the Trump administration and the current leadership
at FDA has been very i think outspoken, very public
that they believe that the work should be done to
(31:39):
enable concurrent coverage decisions with a regulatory decision. So our
intention at this point is to certainly apply for that program.
That program is limited the number of spots it takes
per year, per cycle, but one of the things they
are looking at is the impact and the patient population
(32:00):
and the prevalence or lack thereof of therapies in that space.
And we know for the vast, vast majority of Alzheimer's
patients there is just not any type of therapy available
to them. So that sort of let's call that sort
of path a and then you get the opportunity to
work very closely with CMS provide the necessary evidence around
(32:21):
how it should be coded its benefit category. I think
the benefit category would be that of durable medical equipment
MEAN and so the payment model on that can shift,
but traditionally it's either pay at the time or pay
over a year or thirty.
Speaker 1 (32:37):
Yeah, thirty yeah, I'm thinking of like the diabetes companies.
Speaker 3 (32:40):
Yes, right, And so that the unit's a pretty well
established and we've heard from in our market research, we've
heard from from payers from commercial payers that you know,
chronic therapies for chronic conditions is very tough. So think
about the glps. I'm struggling with the disease. The GLP
can resolve the disease, but I have to continue to
pay for the GAIL and when I don't, the disease returns.
(33:02):
Versus I have a chronic disease like Alzheimer's disease. I
pay for a therapy once and then it's durable for
three to five years, and then really what we're talking
about is driving adherence that the patient continues.
Speaker 2 (33:15):
To utilize the therapy.
Speaker 3 (33:17):
So that would be I think the benefit category there
is what they call the hick picks or the coding process.
You have to determine whether there's an existing code for
what you're doing. Given how the the iniquity of what
we're talking about with is an at home therapy for
Alzheimer's disease, there's obviously not an existing code, so that's
(33:38):
something that we would explore. And then really it's creating
the evidence necessary and CMS was very clear that they said, look,
we have some expectations from medtech companies that one you
do more robust evidence generation in the pre market. Two
that you do it representative of the population and looks
(33:59):
you look an impact, three, that you make it diverse,
and that four that you are thinking about engaging us early.
And we really feel well positioned in that right. We're
the largest study that's ever done in this space, and
being our fifth study, we are obviously very representative of
medicare population because that's what we've included in all of
(34:20):
our studies is the is the age group of Alzheimer's.
We are extremely diverse in our study and what we
enrolled in that in the study, and then we've we've
tried to engage as early as possible. But it's it's
something that we're really going to have to think about
because there's going to have to be a balance between
(34:41):
making sure that we find a way to get this
to the patients that need it, and then we but
that we you know, we price it and we cover
it accordingly. You asked a question about, you know, in
combination that I do think is one of the things
that's so interesting about the safe of the device is
(35:03):
and the and the and the mechanism being as novel
as it is, that I do think it does align
itself for use in advance of other drug therapies, use
in combination of other drug therapies or other therapies, and
use post of those therapies. So it'll all need to
be studied and explored and applied to you know, submitted
(35:25):
to the regulators. But the pre clinical evidence tells us
that there's nothing that would stand in the way of
that being an option.
Speaker 1 (35:34):
Yeah, And it's interesting that you talk about being used
in advance of the pharmaceutical options, and it's in my mind,
I'm theoretically thinking that you could potentially scan for these
patients earlier in the progression. And it almost comes to
a point where could it be where theoretically you could
be scanned for gamma way of activity and basically if
(35:59):
you're seeing in the game away activity go below the
forty hertz, you go on to the therapy or is
that too ston to like think?
Speaker 3 (36:06):
No, I think, well, I think it'll be thought about
a little bit differently, but I think it's I think
it's a really good point, I think, which is one
we are obviously seeing an explosion in the early stage diagnosis.
Speaker 2 (36:17):
Of Alzheimer's disease.
Speaker 3 (36:18):
It's both the encouragement and the education of that from
the lilies and the biogens in the East sides of
the world that are saying, well, our therapies are most
impactful in those patients earlier in their disease progression, and
it's important. Right, there are seven million people in the
United States with Alzheimer's disease.
Speaker 4 (36:35):
Right.
Speaker 3 (36:35):
There are twelve million people with mild cognitive impairment, which
is the earliest stage, ten million of which are undiagnosed. Yeah,
so that's staggering. So one, we've seen new approvals in
biomarkers and diagnostics that is going to make it much
easier to get those patients diagnosed. But I think what
(36:57):
you're going to see is you're going to see real
challenge in two parts. I talked to a leading neurologist
last week at the ai CE and she told me
that she had screened thirty five hundred patients for the
amyloid therapies and four hundred were able to progress to treatment.
That's thirty one hundred patients that are left without a solution. Yeah,
(37:19):
that's an enormous number of patients that are now diagnosed
and looking around saying, well, that's what can I do?
Speaker 1 (37:26):
Well, Actually, I'm just now curious what's the main exclusion factor.
Speaker 3 (37:31):
It can be the risk to the side effects. It
can be the different you know, sort of genetic testing
that occurs. It can be the stage of the disease.
It can be it can be an array of things
that disqualifies them from the amyloid targeting therapies. It can
be other comorbidities or conditions, and so that so one
(37:54):
you have this bolus of patients, you know, these folks
that are in desperate need of it, So to see
more and more patients diagnosed earlier, you're going to see
them go through which is going to increase the burden
to the neurology practices, which they are already at capacity
and struggling. You're going to see of a limited number
(38:17):
get approved. And then lastly, I think what you'll see
to your question is technologies like Spectrius would have the
opportunity to really mobilize the.
Speaker 2 (38:28):
General practitioners and the geriatricians.
Speaker 3 (38:30):
Because what they could say is, Okay, I'm going to
give an MMSC and a blood test. I'm going to
flag that this patient is at risk for or has
Alzheimer's disease. I'm going to immediately get them on spectris
to start preserving cognition and function. And then if we
decide to put them into a care pathway that explores
(38:52):
the amiloid target therapy, great, but that process can take
a long time. So this is an opportunity to be
as early and proactive as possible in getting patients of therapy.
Speaker 1 (39:02):
It sounds like you have quite a busy year eighteen months,
twenty four months, But I'm going to just go even
what else is there? Because you know you are doing
some other pre clinical work and so you know, between
you know, the early clinical work for parkinson disease and
other developments, how do you see the state of neuroscience
(39:24):
in five to ten years and how does cognitive fit
into that?
Speaker 2 (39:27):
I don't.
Speaker 3 (39:28):
This is where you're going to hear real excitement in
my voice because one, you know, as we've talked about
the kind of mechanism of action, what you didn't hear
me say was anything that was specific to Alzheimer's.
Speaker 2 (39:39):
Our story doesn't begin with Alzheimer's's kind of.
Speaker 3 (39:41):
Ends with it, right, which is we believe that we
can drive this biology, which it creates a neuroprotective environment
that we think is very important with those with neurodegenerator
disease and where we're first exploring testing that is in
ad patients, but we believe that there's an opportunity for
that to be impactful in as you mentioned, other degenerator
conditions and PD and MS and Louis body and a
(40:07):
whole other area of nirogenetics. We believe it's potentially impactful
in brain injury like stroke and traumatic brain and concussion.
We believe it's potentially impactful in areas like addiction or
mood disorders or sleep. But we believe that because we
(40:27):
have this incredible flywheel of evidence coming from the preclinical
what we've really started to do is to create what
we're calling brain health collaboratories, which are you know, let's
think about what we have sort of unique to us.
One is we have this incredibly safe, potentially enormously impactful technology.
(40:52):
We have a tremendous amount of preclinical signal coming from
leading academic centers around the world, and we think we're
going to have this various of broad application to it.
So what we want to make sure we're doing is
that we're exploring those in real partnership with leading academic
centers around the United States. So we're going to be announcing.
Speaker 2 (41:11):
Our first collaboratory with the.
Speaker 3 (41:14):
Rockefeller Neuroscience Institute at West Virginia University Medicine that I'll
be coming in the next couple of weeks. But what
that will allow us to do is to not only
do the evidence and research necessary to prepare for an
Alzheimer's launch, to not only think about how we should
explore more broadly in Alzheimer's disease specifically, but then how
(41:35):
should we explore research in these other areas that we
think we've got pre clinical signal for. So I think
it's got an opportunity to truly reshape neuroscience. And I
think we're going to see in neuroscience is like or
in what we've seen in others. Right, medical technologies completely
disrupted cardiology with ablation of racil fibrillation and implannable cardiac devices.
(42:02):
We saw medical technologies non pharmacological, completely disrupt oncology with
radiation therapy and break your therapy, and technologies like novercure.
We've seen it early stage in neurology with deep brain
stimulation and TMS and others. And I think what this
is going to show is in these neurodegenerative conditions. Here's
(42:22):
an opportunity to not only use a non pharmacological, but
a non invasive at home therapy for that, which I
think is unbelievably exciting.
Speaker 1 (42:32):
Yeah, and I tell you what, Chrishan, I'm looking forward
to having you back on again to dive deeper into
those fields. But thank you so much for joining us today.
It was a great conversation.
Speaker 2 (42:41):
Yeah, I so much appreciate the time and the engagement.
Thank you so much.
Speaker 1 (42:44):
Yes, and thank you to our listeners for tuning in today,
and we hope you join us for future episodes. If
you'd like to stay up to date, you can click
the subscribe button on Spotify or your favorite streaming platform.
Speaker 4 (42:54):
Take caress.
Speaker 2 (43:17):
Uses, musings, nomos
Speaker 4 (43:25):
Uses,
Host
Jonathan Palmer
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