Good morning, and welcome to iSelect Industry overview Webinar Series. My name is Teddy Potter, a summer associate on the I Select Ventures team. And I’m excited to talk to you today about our findings and about this presentation and the findings that I came across regarding traumatic brain injury diagnostics.

For those new to these webinars, I selected an early stage venture capital firm in Saint Louis, Missouri focused primarily on early stage companies in healthcare and agriculture. At I Select, we are privileged to live at the forefront of innovation, seeing emerging problems, solutions, and macro trends at their beginning before they make their way into popular culture. We use these deep dive presentations not only as a way for us to better engage with and understand new science and technology, but also to engage with experts and entrepreneurs who are driving change and innovation in their respective fields.

One such macro trend is traumatic brain injury diagnostics, which we will be examining today.

TBI is arguably one of the most complex neurological disorders in the most complex organ in the human body. Recent advances in technology have allowed scientists and researchers unprecedented access to the darkest corners of our brains. TVI, as we will learn today, is a pressing issue for nearly two point five million Americans on an annual basis. For this reason and many others, which we will cover in today’s webinar, traumatic brain injury is of increasing interest to I Select.

Before we get started, a few process comments, we are not soliciting investment or giving investment advice in any way whatsoever. This presentation is general industry research based on publicly available information.

We have invited you to this because you are technologists, thought leaders, entrepreneurs, industry experts, early adopter customers or sophisticated investors that are part of the ISLEK network. We value your thoughts questions, comments and insights into this topic, and we greatly appreciate it if you actively engage during this presentation.

Thank you in advance for your attendance, and active participation.

We ask that you please put yourself on mute for the time being. However, we hope for this to be an engaging and interactive presentation. So if you have questions or comments, please feel free to unmute yourself at any time and provide any commentary.

Lastly, this presentation is being recorded. And will be available for replay in the next few days. With that, I’m pleased to bring you this week’s deep dive on traumatic brain injury diagnostics.

Some of the topics that we’re going to cover today.

The introduction to traumatic brain injury, we’re going to discuss some TBI symptoms. We’re gonna take a look at a study that was done on subconcussive TBI links to CTE, traumatic brain injury diagnostic current practices and then the current gaps associated are going to look into emerging technologies. And then we’re going to take a peek into some of the larger that we see today as far as funding for research and development.

And we’re going to dive just a little bit into market opportunity Then we’re going to move into investment activity, industry influencers, and then we’ll close-up with my closing remarks. And any commentary you all would like to provide Just real quick, some of the initial findings that that were uncovered in this research Like I mentioned, TBI is considered one of the most complex disorders in the most complex organ in the human body.

On an annual basis, direct and indirect costs associated with traumatic brain injury are in excess of seventy-six point five billion dollars There have been some emerging technologies and exciting advancements by means of point of care tests.

For example, handheld EEGs, blood based testing to detect protein biomarkers.

Ocular motility to detect cranial nerve function as well.

Some of these newer findings have revealed that hits to the head not just to concussion, cause chronic traumatic encephalopathy, also known as CTE, commonly referred to in recent news regarding the NFL, their concussion protocol, and some of the professional athletes have issues brain ish, brain issues disorders, neurogenitive disorders that have been scientifically linked to repeated Tvis.

Unfortunately, this is only diagnosed after death. There’s a protein called tau, TAU. So when an autopsy is conducted, these brain tissues are extracted, and there’s this protein cow that’s identified.

Cow is the protein responsible for killing brain cells.

Not gonna talk a whole lot about that, but that is a very interesting topic.

Something definitely worth looking into, we can get to that later. And newer findings show that concussive brain injury reprograms genes, which could lead to predispositions or neurological and psychiatric disorders.

And also that genomic information from peripheral leukocytes has the potential to predict TBI pathogenases.

This is very significant.

If we can link this to other existing or pre existing or potentially future cases of neuro neurogenitive disorders.

This would be an incredible discovery.

And lastly, artificial intelligence and high performance computing, we’re going to dig into that a little bit with one of our initiatives.

But really try to develop a comprehensive multimodal understanding of traumatic brain injury.

Alright.

So we’re gonna dive into a few slides that are gonna discuss the background of TBI.

So let’s let’s take a quick a quick little test. Active engagement from our group here is welcome.

Who can spot the injured brain.

One on the right.

One on the right.

What do you think, Mike?

That’s what I would say too. Right.

You guys?

Negative.

It’s the brain on the left. So these are CT scans.

Conducted of the brain, and the left is post TBI and the right is a baseline healthy brain.

What’s the is the white tissue some sort of amalgamation of a certain type of protein or tissue What is that tell what’s that telling us? That’s obviously a telltale difference here.

So there’s a couple things.

One, I cannot scientifically read into read into this. But a couple issues occur, which we’ll touch on in a little bit.

There is excessive swelling, for example. There is leakage of blood across the blood big blood brain membranes.

And then there’s also damage to nerve fibers as well.

And so what we’re most likely seeing, and I am most likely ninety-nine point nine percent wrong.

Is what I referred to guys. Yeah.

Defusal diffusion axonal I’m totally blank on it, DAI, diffusion like tunnel injury, I believe.

It’s essentially when it is a closed So there’s no puncture.

It’s what happens when your brain is essentially shaking around and bouncing inside of your head due to some type of traumatic event.

And what that does is causes excessive swelling. Anyways, that’s my best guess.

Alright.

What about now?

Who could identify some of these folks? Tracy Morgan? Tracy Morgan. Jordan. Good morning. Good morning. Steve Young.

Steve Young.

Okay. So on the top left, this is Tracy Morgan, as you all said.

Was diagnosed with severe TBI following a horrific car crash in June of twenty fourteen. On the bottom left, we have Nate Anderson, who is a member of the U. S. Army forces. He was not properly diagnosed with TBI along several in addition to tens of thousands of other US military personnel.

And because he was not able to receive the proper diagnosis, he suffered immensely.

In the top right, we have Pamela.

Last name is undisclosed, was involved in domestic violence for years before finally coming forward and being diagnosed with multiple Tvis.

And then obviously in the bottom middle, Steve Young, professional qualifying quarterback from the San Francisco 49ers, has spoken out recently about his personal thoughts regarding head trauma, brain injuries in the NFL and also in collegiate and high school athletics.

And then on the bottom right, this is very unfortunate.

Not that none of the other ones are.

Pediatric TBI is incredibly difficult to diagnose is far more prevalent in children that are under four than any other age segment And so what’s really alarming here is that your child may be suffering from some type of traumatic brain injury, some type of event, but lack of ability to communicate, lack of ability to be able to conduct proper testing provide proper answers.

The reason why I wanted to show you these pictures is because as we’ll discuss, this is a silent epidemic.

And these folks don’t show any, excited for Steve Young here.

You folks don’t show any sign of any immediate trauma. But what lies inside the brain is largely a mystery. And hopefully we’ll be able to uncover it relatively soon.

So what is TBI?

Got my my friend down there in the bottom right, he’s shooting a small. It’s a shoulder fired rocket.

Operates upon detonation.

It creates thermovaric concussions, essentially sucks all the oxygen out and creates a massive blast in a confined space. So as most of you all know, this is a sudden trauma incurred that causes damage to brain tissue.

There are multiple stages of TBI. We got moderate, mild to severe.

An overwhelming majority of the cases of of traumatic brain injury would be classified under the mild category.

Main mechanisms of injury include a blow to the head acceleration, deceleration forces, projectile and then concussive forces.

So how does TBI really affect the brain?

So there’s two types of TBI related damage that’s confined.

And then there’s, which would be referred to as focal, and then there’s a widespread damage, which would be referred to as diffuse.

The onset, there’s two classes primary and secondary.

The damage under primary is immediate.

Within several seconds to minutes, and then the secondary damage occurs gradually over hours days or weeks.

A couple of primary symptoms would include a concussion, skull fracture, contusion, diffuse axonal injury, which is what I was trying to recall a few moments ago and then penetration.

So you say concussion is a symptom, not a TV, not a mild TBI in and of itself?

No, so a concussion would be potential loss of consciousness for a matter of seconds to a matter of minutes.

Or if you enter a comatose state could be days or months.

But what’s really interesting here is that we’re gonna discuss this here here in a minute.

Just because, say, I were to punch you in the head.

Right now, jump across the table and hit you, Tom.

I would never do that.

But you were not you would most likely not get a concussion because I’ve got a really soft punch. But that blow alone can disrupt very microscopic fibers in your brain, that over a period of time can build up and result in what we refer to as CTE.

And we’ll talk about subconcussive study here in a moment. And then the secondary, later onset, intracranial hemorrhage brain swelling, increased intracranial pressure, brain, hypoxia.

What I believe we saw in that picture, David was increased intracranial pressure.

And again, I could be totally wrong.

But that’s my best guess.

So some of the symptoms. So mild TBI and then is essentially, like I said, the majority of cases. It’s a silent epidemic.

Going back to the pictures, yes, some of those were more moderate to severe.

But really there’s a lack of visible physical science.

So just because, you know, Steve Young is laying on the ground or our friend Nate Anderson, suffers repeated concussive blasts that jarred his brain.

There might not be visible effects. And this can be often unnoticed and overlooked, but have some significant cognitive psychological and behavioral impairments.

And then, so some of the symptoms of the mild TBI, and I’m sure that most of us have had some of these at some point in our life, if we’ve played high school athletics.

Mild headache, blurred vision, behavioral or mood changes, trouble with memory concentration.

Tentiveness or thinking. There’s a number of symptoms here, but it is a disruption of our cognitive state.

So looking into the moderate to severe TBI symptoms.

So these would be in addition to the aforementioned symptoms. An unrelenting or worsening headache, for example, nausea, repeated vomiting, slurred speech dilation of pupils, tingling, numbness and extremities, restless misconfusion to agitation.

So this is just a more, a hyper set of symptoms, a more pronounced set of symptoms.

And there’s been a lot of back and forth in some of the research that I came across.

There were folks that made claims back in, you know, early to mid two thousands that said, traumatic brain injury was linked to x, y, or z, neurodegenerative disorder or disease.

Then there were studies that said, those initial studies were wrong. And now what I have been able to uncover is that there is a more focused, scientifically backed through what will talk about here in a little bit, blood based biomarkers and additional biomarkers in the human body.

That are able to be linked to chronic traumatic encephalopathy dementia, Parkinson’s disease and Alzheimer’s disease. And David, I know.

You did Alzheimer’s disease diagnostics last week or a couple weeks ago. And I think you’re doing the therapeutics next week. I think there’s a lot of Carrie, and I’d love to share some of the some of the information that I came across with you. I think it’d be pretty beneficial.

Okay.

This is one of the more alarming studies that I came across.

And a reason for concern for some of our younger members of society that’s participating mainly in athletics.

So there’s a study done on Boston University by Dr.

Lee Goldstein. And the results were published in January of twenty eighteen.

And, essentially, there’s a lot of words on here.

But the key point here is his findings provided strong causal evidence linking head impact to TBI and early CTE independent of concussion.

So This is significant because Tom, I may have hit you, and then you maybe have shaken up a little bit, but you may be fine and can continue to carry on throughout the day.

That still does damage. And it might be a minor damage, but that’s built up over a period of time.

If we look at some of our high school athletes and collegiate and professional athletes, just because you don’t get a concussion doesn’t mean that damage wasn’t done. And this is incredibly significant, especially if these studies in fact can be linked to other neurodegenerative disorders.

And then obviously the development of CTE down the road. There are so many second and third order effects of TBI.

Like I said, it’s very alarming. And so, the more information we can get and really our level of understanding behind all this is is what is very critical.

And I think that’s where we’re currently lacking as a society.

Petium, just done, there was also a study at the Cleveland Clinic that found the same thing too that was done in conjunction with Uphaba and Rochester’s Medical Center. Okay.

But in that study, they were looking at the and their their predictive factor was damage to the exterior barrier Right? Right. Okay.

What are the predictive factors for CTE that that would be in the study? Is it it looks like external factors balance is one of them. Are they looking at changes in the biochemistry of the brain or the production of TAL to to validate this? Yeah.

So that’s where the science really takes off.

We’ll discuss a couple of instances. So and this has really taken off in the past I’d say eighteen to twenty four months. This is it’s been a topic of interest for several years, but recent advancements have uncovered links between various proteins in our in our blood.

And if there is an increased level, that is uncovered through some of these initial testings. One of them just cleared FDA approval and will be commercialized in twenty nineteen.

But when you’re able to look and identify these proteins, you can do a far greater with higher accuracy test to say and confirm whether or not an individual did suffer a traumatic brain injury.

And so I, obviously, I can’t go into all the science of it.

But the quantity in the level of these proteins in the blood is directly linked to intercranial damage or maybe there’s no puncture or it was an open wound or a closed wound, Obviously, if it’s open when you know that there’s most likely gonna be a traumatic brain injury.

But this is gonna be able to provide a more definitive response.

And so I didn’t look too much into Tau, but I did speak with Susanna Rosie from UCSF.

There is some incredibly fascinating work coming out of UCSO.

And I’m really excited to touch on that here in a little bit.

She talks about well, in her email response to me when I invited her to this presentation, she mentioned she was going to a conference specifically regarding TOW. So I’d be very interested to hear really what comes out of that.

And unfortunately, like Alzheimer’s, it’s one of those things where we can really only uncover this after death in an autopsy. So, that’s where we can confirm.

An individual did have CTE. That was probably very long winded Yeah.

No.

But I guess I could just I just Probably answers.

You answered my question.

Thank you. Yeah. Yeah.

I It’s a great question, and we’re gonna hop into that here in a few minutes.

So we’re gonna move into current practices.

I’m not going to spend a whole lot of time on this because I want to get to you for the sake of time some of the other parts of this presentation.

If you’ve ever had a concussion, you know that a lot of the diagnostics have been relatively qualitative.

So you’ll undergo a standard history and physical exam. Assess your motor skills with various tests as I’ve listed here in the presentation.

We’re gonna just briefly go into a glasgow coma scale. And then I’m not going to go into post traumatic amnesia, but it’s a period of time.

After the incident based around memory and recollection.

So Moving into more of the quantitative screening and practices, really this is gonna be based upon with severity.

And that’s gonna be up to the discretion of the medical care provider at the either emergency room or specialty clinic. Obviously, if like I said, and I’m not trying to make light of this, but those folks that haven’t open wound on their head, or have a pretty significant amount of time in which they are unconscious.

Will be more likely to be assessed with follow on screening. So like CT computerized tomography MRI, and then we’ll just briefly look into advanced imaging technology.

It’s not going to spend too much time there.

So this is the Glasgow Comascale. Very qualitative.

Ask you a few questions if you can respond in a certain amount of time you’re given a number.

And in that number, these numbers are collected and then summed up, and it’s between zero and fifteen.

And so obviously not testable the individual cannot speak or move six or the higher number in the category would be in reference to an immediate response, a highly coordinated action and so on. As you can see on the right, model excuse me, mild moderate and severe.

This scale is listed.

Some of the current limitations, and it might sound kind of silly, but There are a lot of instances where an individual will be intoxicated, drugs or alcohol, get the car, get the collision, fall bump its head, so on, or her head. Individual with shock, low blood oxygen, and then also children Like I touched on a little bit, this is very difficult to assess in children, especially with ones who maybe not be able to communicate or understand what you’re saying.

But there are additional studies for those folks as well.

So, head CTPMs and MRIs, these are essentially aimed at identifying macroscopic issues or macroscopic lesions.

These conventional imaging tests are limited in their capacity to assess the finer points. So microscopic white matter, for example, which is commonly associated with diffuse axonal injury, DIA.

DIA is caused by acceleration and deceleration forces that are incurred on your brain. So in a violent collision, for example, or another jarring injury.

What’s really alarming here, and this is really a point that I want to make sure is driven home.

Only a small percentage of patients with mild TBI demonstrate visible pathology, such as fractures, contusions and hemorrhages on the head.

There have been some studies that have confirmed this. These numbers are from the CDC.

They examined four thousand patients. Five percent to ten percent of mild TBI patients with a glasgow coma score of fifteen.

Had an abnormal head CT.

And in a similar study conducted only between twenty percent to thirty percent of patients with initial Gcf score of thirteen had an abnormal head CT. And so really what that’s saying is that there are folks that underwent some type of traumatic event, and their numbers do reflect some type of score.

But in very limited cases, if it is not a physically obvious symptom, these individuals are not able to be diagnosed properly, and only five percent to ten percent of them, for example, are able to be diagnosed on current basic emergency room imaging processes.

Some of the other points, when you have a CTP at MRI, there’s potentially adverse effects of increased radiation exposure.

And then again, recent advancements in technology advancements in machine learning and artificial intelligence are going to seek to really refine this and and limit this diagnosis.

But These test produce results.

And at the end of the day, those results are only as good as the individual that is assessing and analyzing them.

And so there’s unfortunately a wider scale of variability here.

Based upon the individual’s expertise and background. Let’s see.

Also, additionally, some of these more advanced techniques, obviously CT scan MRI are available in most trauma clinics, emergency rooms and hospitals. But some of these more advanced imaging capabilities are incredibly expensive, costly, and not adopted by every facility.

So that in and of itself is an issue.

Teddy, about a year ago, I had a concussion. And the way they were able to diagnose it was because my electrolyte balance in my blood got so out of whack. Mhmm. And then they came back and did blood tests every week for a week, three weeks until they’d like balance sell back out. But they were looking for external, and they couldn’t actually identify the concussions of any type of meats that were just looking for external effects or symptoms of it to be able to diagnose it?

Yes.

I mean, I can speak from personal experience.

I’ve had several concussions. And my experience is in the military. I’m sure don’t help that stuff. But I’ve never been officially diagnosed with having a concussion. But I’m sure you guys have had concussions before.

So that in and of itself, I guess severity or degree of it of the traumatic event, warranted follow-up hospital visits I don’t know what Well, for me, the sound of my endurance training, we had to keep an eye on on that.

So that was where I showed up within my electrolyte balance. And that was that was the only physical manifestation that they found of it. So Interesting.

I’ll have to take a look into that. That’s neat.

Okay.

So again here are two images. On the left, we have a CT scan twenty year old patient with traumatic brain injury.

Here, we can clearly see that there is an issue with this gentleman’s left side, which is head On the right side, we have an MRI.

So there’s two different images side by side. Showing that the different imaging capabilities that we have.

Some of the advanced imaging technologies.

I’m not gonna really spend too much time on this.

Defusion tensor imaging, quantitative single photon, emission computed tomography, which is actually pretty cool. We got a picture of it coming up next. And then diffusion pertussis imaging.

These are just I’m not trying to downplay it. And these are incredible advancements, but it’s not where I’m going to spend the bulk of my time.

Is there anything – of these three, is there anything that’s like the real, like, the time messed up where you’re just, you know, on the field or in the or the battlefield, I guess you might also add. Yeah.

Like, forty year blue dry ball kind of thing or Yeah.

Like, I could diagnostics. Yeah. So there’s like ocular motility, which is assessing, like, the movement of the eye.

And I mean, that’s all always been interesting. You know, when you get a concussion your trainer on that athletic field will, you know, shine a light in your eyes, see how it reacts, and and watch the movement of your eye in relation to its ability to follow a finger, and for example, that’s one of the issues though is portable objective technologies and diagnostic capabilities.

We’ll touch on that here in a moment. Again, I absolutely want to understand not down downplaying these imaging technologies at all.

I think they’re incredibly interesting, and they’re going to be a very important part for the diagnosis of TBI and other neurodegenerative disorders. So just taking a quick look.

So Dr.

Jets Jensen for this top part, He did a study at the Medical University of South Carolina. And he was able to find that pre and post athletic season in high school football athletes, there’s sufficient microstructural changes in the brain even without a concussion.

So again, coming back to that subconcussive injury.

Again, that is particularly alarming just because this has been such a misunderstood field for far too long now.

On the bottom, we have SiriusScan.

They’re a company, a pretty large scale company.

Four images here, it essentially creates a three image based on two hundred and sixty two thousand data points, very fascinating and creates a very all encompassing picture of an individual’s brain.

So the current diagnostic gaps Again, subconcussive mild TBI detection.

How do we know what’s really going on in somebody’s brain?

Is there anything that we need to be alarmed or concerned about regardless if they have or have not had a concussion. And again, only ten percent of abnormalities associated with mild TVI are detected in CC or MRI.

And so this unfortunately leads to a lot of undiagnosed or misdiagnosed.

And then what’s really unfortunate here.

Say you do find yourself with a brain injury you are. In a car crash or whatever the mechanism of injury is.

You do get a CTR MRI that shows no abnormalities And then, for example, our high school athletes may be clear to go out and continue contact sports. That is a point of major concern, and then which we’ve touched on previously.

Continued monitoring capabilities, so things like wareables, halo devices, things to continuously provide real time feedback, various things, various metrics. And then really high cost and radiation exposure with the current imaging technologies.

I I just want to make a quick point here. I don’t fully understand.

I mean, I could obviously be totally wrong.

I don’t think the radiation exposure from like a one off head CT scan is significant. I don’t have any quant quantitative data to support that just based on a couple things that I’ve read.

But obviously over time, and exposing somebody can have adverse side effects.

Genomic biomarkers in Mike, we were talking about this.

We’re gonna go into this here in a second. Very interesting.

These technologies have produced some, pretty significant and meaningful studies.

As far as objective diagnostics. And then we’ve got memory failure, restoration recovery.

And then pediatric TBI A couple of the reports in articles that I came across, cited, a lack of research and studies around child TV or pediatric TDI.

So emerging technologies.

This is from doctor Neil Harris from the David Geffen School of Medicine at UCLA.

TVI affects nearly one point seven million individuals each year.

Just a side note, I’ve seen this number kind of fluctuate a little I’ve seen anywhere between one point seven and two point five.

There’s a need for non invasive biomarkers to indicate the degree of injury. Fix functional outcomes and advise how long an injured patient must remain away from sports or work before resuming activity.

One of the things that the folks out of UCLA have been able to identify is lysophosphatidic acid or LPA. Is associated with major regions of brand pathology and found to be in the bloodstream in higher concentrations after brain injury.

And then advancements in mass spectrometry have enabled a measurement of discrete changes in lipid distribution within brain slices.

Banyan biomarkers.

So if you’ve done any research or had any interest into these biomarkers, you’ll know that venue biomarkers is the leader currently in the United States.

They’re really the pioneer in the development of blood based biomarkers for TBI. They’ve developed brain their brain trauma indicator, also known as PCI.

High sensitivity of ninety-seven point six percent and a high negative predictive value of ninety-nine point six percent And really the whole premise of this is So you do suffer some type of traumatic event.

There is concern about a brain injury.

This test can tell you whether or not you need to go and get a CT scan MRI or another advanced imaging process.

They identified two sitting brain two brain specific protein biomarkers. Glial fibrillory acid protein came up quite a bit in my research.

And there’s a couple companies that are utilizing this specific protein, also in conjunction with a couple other proteins that we’ll talk about on the next slide.

Bottom line here is blood based biomarker.

FDA is granted approval of this brain trauma indicator in twenty eighteen.

And they are going to be taking us to market in twenty nineteen.

And again, this is going to tackle issues such as excessive emergency room costs, unnecessary care and exposure to radiation So like I mentioned, this company is looking at two proteins.

Conducting a proteomic analysis on HFABP.

What company?

I’m sorry. My apologies. This company is out of Europe. They’re called Advanced Brain, Companion Diagnostics.

I couldn’t find any financial information on them.

I believe that they’re backed by a larger medical or pharmaceutical company.

This has not been approved in the United States with regards to the FDA.

But essentially what it is, point of care tests, one drop of blood, And it can tell you whether or not you need to receive follow on treatment within ten minutes with his best fifty percent at forty six percent sensitivity of one hundred percent This is interesting, and this is unique because, for example, the Department of Defense is interested in something like this because this is a battlefield tool that can be utilized, essentially, in combat or shortly thereafter.

And then also here more in the civilian perspective.

EMT’s emergency rooms can utilize this in addition to athletic trainers at the professional collegiate and high school level.

Next, we’re gonna move into funding initiatives. And this is this is what I found to be some of the more interesting pieces of this presentation.

First and future is presented by the NFL.

They have allocated several hundred thousand dollars to provide for startups that come in pitch to them.

I believe they do it just before the Super Bowl winners are awarded anywhere between fifty thousand dollars and one hundred thousand.

Dollars The NFL is looking they’ve got an issue with traumatic brain injury.

They’ve got an issue with concussions.

And this is no secret if you’ve really paid attention to you know, things that have come up within the news.

Looking to identify technologies that will advance athlete health enhanceability to collect, analyze, and distribute biometric data, and then identify technologies to improve care and accelerate recovery.

I think this is a very very solid approach for the NFL shows, anyways.

Did you see any initiatives involving the NCWA?

I didn’t might’ve been at the end. You know, Bell is a slightly different case. You know, players getting paid millions of dollars. Yeah.

On educational institution. They’re not using it to raise money for academics.

Right. Seems like the way to be taking it seriously or more seriously than you as well.

I did come across NCWA a couple times, but I did not do any specific research into their initiatives.

But yeah, totally agree with you, Tom.

Absolutely.

Do you do you see like the I mean, in terms of the opportunity for like a diagnostic versus like preventative technology like where do you see like the opportunity from, like, an investment standpoint? I guess, like, my quite as a guy, I know there’s a company that I’ve been working on helmets that trying to prevent TBI?

I mean, do you think that there’s in terms of an adoption of technology like this or like the ones you’ve mentioned here?

Is there is there a greater jump to be made in a prevention or is there a greater jump to be made in a diagnostic perspective? So that’s a great question.

And I came across this several times. And the major issue is ES prevention is great.

But if we can identify the pathology of TBI and understand some of the more underlying, I guess from more of scientific approach, some of them more underlying issues within the brain.

I think that will greatly lead to more preventative measures, therapeutics, drug discovery, things like that.

We’re still trying to understand really why, you know, trying to get trying to This stuff is complicated. And there’s a reason why it said that this is regarded as one of the most complex disorders or issues within the most complex organ within our body.

There is so much more to discover within this.

I think short term preventative measures like helmets are great.

I think limiting child, you know, interaction in athletics where contact head to head contact is an issue. I think that should potentially be addressed.

I know like the NFL is in the NCAA. They’ve got specific rules and stuff. You can’t there’s nothing you can invest in.

And the evidence is there, the data is there, that TBI and events associated with brain injury. It’s not slowing down.

Where most of the cadence we jump from? Are they mostly from contact sports?

Eighty percent of hospital visits are in the segment of the population that’s nineteen years or younger. And are associated with sports related injuries.

Okay. So if you’re an adult who’s not in the military and not playing professional sports, your likelihood of getting TVIs probably more related to a random event, car accident or Yeah. Yeah. Absolutely.

A car accident.

Unfortunately, domestic violence children, shaking of the child, physical punishment, things like that. You can essentially get a traumatic brain injury from bumping your head on the Dasca.

My wife had a family friend whose three year old wasn’t wearing a bicycle helmet, was going, you know, like less than two miles an hour on a was just over four years old, fell bumped his head.

No big deal.

The kid ended up dying. So when they tied it back to that that specific incident.

So this is gonna take you lay off topics here. But when you look at this, David, presentation on Alzheimer’s. Like, the cause of Alzheimer’s at least what we think right now is to an overexpression or too much amyloid beta in your brain. Right? They’re mainly of the in the cloud version in the plane.

In like neurofibers. And so when you – it’s traumatic brain injury in the presence of tau, is that the correlation between The two things from a from a causation standpoint is the production of tau from the brain injury causes the the brain to somehow stop during the amyloid beta? I wouldn’t confidently do it. So the, like, the Alzheimer’s cause, there’s so, like, unknown that it’s Like they like, there’s a strong like, there’s a strong correlation between like amyloid beta and and these like, nerves are going tangles in the brain that are only diagnosed truly like an autopsy, the after death.

And those are like those are like the pathologies of they don’t know what caused. Again. Yeah. Okay.

So I don’t know if I like to say, it sounds like in TBI, you’re saying like this nerve to voice angle is like a curve — Mhmm. — and that that’s some of the positive brain to to deteriorate — Mhmm. — to TBI. I guess the difference here that TBI has something past one clear cost that — Yeah.

— there’s a physical You said that there’s a mental physiological manifestation of which you can point to the to call the Right. I think you’ve had numerous concussions which has caused your brain to deteriorate in this way.

So I think the way to the way that I see it in my in my head, and I I totally agree with you, David.

So you can incur a brain injury traumatic brain injury, for example, and you can incur mild traumatic brain injuries over time. And that would lead to CTE ultimately, which would then significantly increase the amount of tau due to the dying brain tissue.

So I think what we’re what we’re gonna see here in the next couple of years based upon some the discovery of these biomarkers is that things like depression.

If I had depression, for example, why do I have why do I have depression?

You know, is is that gonna lead into something else, something further down the road?

Do I take a qualitative test that said, okay, I’m gonna ask you five questions, ten questions, whatever.

Yes, you have depression, no, you have depression, it’s really hard to really get to a definitive objective answer in diagnosis.

I think So there’s also a genetic — I’m sorry, a genomic approach that they’re looking at this as well. I don’t have a whole lot of information that I Yeah. Yeah.

That was another question I had.

You said that there’s evidence of the concussion. Contess of Brian and Drew reprograms the gene. So then the next question is just an expressed self R and A somehow?

Yes, I did. It does. And I read a study. I didn’t cite it in here just because there was such a lack of information on it. But there was a study and I think it was the MI RNA.

I can’t remember if I’m RNA.

It was M something RNA.

Anyways, yeah, there was a link with concussion and traumatic brain injury and MR. Am hard at I mean, so that makes me wonder whether there’s an opportunity for some cofactor in this space too.

Well, it always meant Lance. The second place they were headed is neurological disease. I mean, yeah. I don’t hers being with data within ten minutes. So Yeah.

So international initiative for traumatic brain injury research.

This is a great international organization looking to build upon research.

UCSF, as I mentioned, they’re doing some absolutely phenomenal studies.

They’ve got a program called TBI endpoints development, which is in conjunction with this is where it really ties into my lab presentation on the joint warfighter medical research program.

There’s a lot of government funding that is going to this. There was a brand initiative that Obama announced in twenty thirteen. Which increase the amount of funding for things like traumatic brain injury, neurodegenerative disorders, memory restoration, things like that. There’s some pretty odd, far fetched ideas out there.

For example, brain computer neural networks and interfaces, and I like that stuff is wild. And I’m not even gonna really go into any of that stuff.

Both, how do you communicate with somebody that is unconscious?

You know, how do you assess the level of damage in their brain when, you know, you might not have access to things like this portable device or advanced imaging and so on. And so it’s really fascinating stuff.

Just the speed of diagnosis improved, really quality of outcomes and reduced the cost of care, Yes.

So first and foremost, there’s a lot of indirect costs that are associated, well, a lot of direct and indirect costs. On an annual basis, over seventy six billion dollars per year.

And a lot of that is attributed to indirect cost man hours loss.

And things along those lines.

And then the direct costs are the testing and follow on testing that needs to be conducted.

When if we can just provide this simple test to say whether or not these proteins are evident in this blood sample, that you need to proceed with further testing. That could significantly decrease the amount of cost going into this. And so I think it’s definitely something worth looking into.

The congressionally directed medical research programs and then joint warfighter medical research program.

The other week, we discussed JPC6, which is combat casualty care. And so there has been one hundred and twenty five million dollars in — this was for fiscal year twenty eighteen, defensive per creation budget specifically looking into psychological health and traumatic brain injury.

And JPC six, these are some of the categories that they’re looking into.

But I try to speed it up a little bit. This is very cool. This is very interesting.

And I would love to spend far far much more time looking into this. There’s this program called Active Advanced computational and translational initiatives.

The Department of Veterans Affairs allocated twenty seven million dollars for fiscal year twenty nineteen, which starts on October first.

Specifically to this study. This is conducted in conjunction with several institutions. Around the United States.

Some of the leading academic scientists and researchers from these institutions are simultaneously working on this. But bottom line here, The Department of Energy has these incredible supercomputers, and they have two of the most powerful supercomputers in the entire world.

And these are computers that can essentially conduct millions of billions I can’t even fathom what that number is of calculations per second.

And so what it does is this allows them to integrate a significant amount of data.

And there is no other healthcare system in the United States that has more health care records, more health care data than the Department of Veterans Affairs. So what we’re going to see here is an unprecedented integration of next generation artificial intelligence, big data, high performance computing, multimodal diagnostics, diagnostics.

I I I apologize. I don’t know why data is on there again.

This is incredibly fascinating. So they’re gonna look at things like patient history, we’re gonna look at things like CT MRI. Gonna take a more multimodal approach to look at proteomic and genomic biomarkers, things like that.

And then they’re going to apply incredibly advanced algorithms and utilize artificially, artificial intelligence based technologies in conjunction with these supercomputers. And I don’t know what they’re gonna find.

On my own time, I’m gonna continue to follow this, because it’s just incredibly fascinating.

But again, this is not a one dimensional issue. This is not a, hey, here’s this, and here’s this symptom, and here’s this diagnosis. That’s not the case at all. It’s going to look at a wide range of metrics for this.

Just put this in for fun. So this is Summit. This is at Oakridge National Laboratory.

Oakeridge National Laboratory is part of the Department of Energy, which is essentially headed by Rick Perry.

Oakridge is down in Tennessee.

And this is the most powerful supercomputer in the world.

That data are all gonna be publicly accessible once they start to have outputs of that?

Yeah. Absolutely. And so I believe this is a five year study.

And what this is gonna do is provide immediate diagnostic and blanket on the word. Anyways, this is going to provide immediate results for military members, their family.

And then for the rest of the civilian population as well. So, like, just because I was in the Marine Corps and my brain got scrambled because I was working in tanks constantly. And the concussion and the blast and the noise and everything, I guarantee it jarred my brain in some facet.

Anyways, that instance is not necessarily different from, you know, your head trauma that you received or the head trauma that you received.

It’s all going to produce relatively similar end states.

And some of this on a cellular level, some of this tissue damage is relatively shown to be relatively the same. And so it doesn’t matter if I was in the marine corps or or you were a gymnast and you hit your head equal sign, it’s it’s the same thing. So is gonna be overlap in various different market segments.

So the market opportunity, we’ve touched on a lot of these.

I don’t have any cool charts or any beautiful data or anything like that. And I’m not paying several thousand dollars for these reports, but this is all open source information.

Seventy six billion dollars in direct and indirect costs annually, one point seven million people annually in the United States sustain a eight type of traumatic brain injury.

Am I going up or down?

What’s up? Is it going up or down?

The numbers that I find are going up.

And the reason why? I’m not sure. I I don’t know.

Thank you, Peter. And people like people’s parents are pulling them out of, like, contact stores and stuff.

To a high school, things like that. It’s because they’re weak.

Hey, man. I mean, I’m your brain’s gonna fall apart.

I can’t do it either. I’m totally kidding.

Hundred percent Children under under the age of four.

Oh, so this is important.

These numbers every single article document journal, whatever that I found, these numbers fluctuated a little bit, but they were all based around studies conducted in twenty thirteen. So this is not twenty sixteen-seventeen or eighteen.

This is not incredibly immediate or relevant data.

I couldn’t find anything other than this.

And I’ve spent plenty of time looking.

So children under four, adults over seventy five.

Also over seventy five have the highest rates of TBI related hospitalization of death, things like this due to falls, for example.

Two hundred and thirty five thousand and fifty thousand hospitalizations and deaths.

Thirty percent of entry induced deaths are related to the traumatic brain injury itself.

That’s a pretty significant number.

Approximately seventy five percent and this is important classified as mild TBI.

And then I’ll let you all read that last bullet point. We’ve already touched on it quite a few times today.

I kind of want to keep pushing because we’re pretty much out of time. These are some of the companies that I’ve identified.

This is a breakdown of these companies how much they raised the date, they have last raised grant funding, investors in the field that they operate in. Ocular Motility is interesting.

And then there’s also measurements of intracranial pressure, bleeding detection, so on and so forth.

There’s a company called Neuro, which I would take a look into.

So again, this is a company that’s developing a product to enable communication to meeting capacity to the patients and doctors.

These are some of the industry influencers that I found in some of these – most of these folks I reached out to.

We’re not able to attend closing comments.

Where should we consider and how should we strategize for investment?

There’s a lot of grant money that’s being pushed towards the research and development of this.

Spinouts from academic institutions would be a great place to start.

Cost efficient portable detection solutions for employment and high school athletics in combat, platform technologies for data wearable sensors.

Is this something that Apple is going to have on their Apple watch in ten years, for example, or whatever?

The latest craze in real time modelingering platforms is recommended for further exploration.

I’ll be honest. This is incredibly heft and cool. And I would highly recommend continuing to look in this. I think I think not looking into traumatic brain injury would be a miss.

And there’s, especially with these advancements in the technology that we have and especially because of the blood based biomarkers, the proteins we’ve identified and this multi pronged approach to incorporate genomic analysis as well.

Very fascinating.

I would avoid capital intensive non portable equipment.

And then I will also avoid incremental progress. So things like accuracy increases a few percentage points. I don’t think that’s interesting.

I mean obviously if you’re going from ninety five percent to ninety nine percent That’s – I mean, it doesn’t really get too much better than that. But if it’s the company ABCD or ABC Diagnostics, accuracy was, I believe, forty six percent anyways.

I would recommend looking into these companies incredibly fascinating.

I know you guys aren’t really interested and I don’t think this really fits in your thesis, I think it would be a good adoption into the thesis. And Yeah.

Anybody have any questions? I would be more than happy.

We’re pretty much out of time.

Anyway, any questions, comments?

Very interesting. Very good work. Thank you. Excellent. All right.

Everybody on the line and everybody tuning in time.