Wearable Neurostimulation Benefits

Daniel Powell [00:00:01]:

Have you ever wanted to go behind the scenes of a medical device company to hear about the ups and downs and ins and outs of taking an idea from concept to market? Well, I'm Daniel Powell, CEO of Spark Biomedical, and I'm joined by my fellow founders, Dr. Alejandro Covalin, Chief Technology Officer, and Dr. Navid Khodaparast, Chief Science Officer. This is Spark a Conversation.

Daniel Powell [00:00:24]:

I think what was most interesting is how fast, the effect has to alleviate withdrawal.

Navid Khodaparast [00:00:32]:

Well, you have to go fast. Right? From the beginning, we knew, you know, again, these are people that are coming in and they're in high distress. You know? Sometimes they don't wanna be there. Just checking into a detox facility and going and receiving treatment is already a huge hurdle. Right? And some are just like, you know, ‘I have to do it.’ You know, ‘This is my time.’ But for most, it's like, this is very hard.

Navid Khodaparast [00:00:56]:

So you think about that, and then you're saying, ‘Here are your different treatment options, and here is a device that's in a clinical trial.’ Right? ‘You wanna try it out?’ And from that standpoint, you have to think of the patient and say, ‘Can this take five hours for them to feel relief? No.’ Or else they're gonna say, ‘You know what? Thank you very much. I'm out of the study. Can I have buprenorphine?’

Navid Khodaparast [00:01:22]:

Right? Because that's a pill. They throw a pill down and they're good. Or it's a patch, or however, it is.

Alejandro Covalin [00:01:26]:

But it takes forty-five minutes. Well, how long does it take to start working?

Navid Khodaparast [00:01:29]:

Buprenorphine takes a couple hours.

Alejandro Covalin [00:01:32]:

A couple.

Navid Khodaparast [00:01:29]:

A couple hours.

Daniel Powell [00:01:33]:

So when we looked at our study, our primary endpoint to have a significant clinical effect was one hour.

Navid Khodaparast [00:01:40]:

One hour. Yeah. And and and significant. Right? Fifteen percent reduction, which is what the FDA considered clinically meaningful and what the literature supported.

Daniel Powell [00:01:48]:

Fifteen doesn't sound exciting to me, though.

Navid Khodaparast [00:01:50]:

It doesn't, which is why we crushed it and we got forty five percent.

Alejandro Covalin [00:01:53]:

In the first hour.

Navid Khodaparast [00:01:55]:

In the first hour. And then it continued to go down over time. So, yeah, it was crucial that we hit that mark within that first hour.

Alejandro Covalin [00:02:03]:

Very fast.

Navid Khodaparast [00:02:04]:

So, yeah, when we were looking at that first hour, it was, what, do you remember the first patient we had in our FDA trial? Right? And methadone user came in. Methadone is one of the hardest drugs to detox off. You can, it's, for most people that are on heroin, you’re talking about a five to seven day detox. Methadone could be one to three to four weeks of acute detox, and that was our first patient.

Alejandro Covalin [00:02:30]:

Your system, and you have to get rid of it.

Navid Khodaparast [00:02:32]:

That was the first patient we had. And, you know, the good news was the device worked like a champ. The patient the withdrawal scores came down. We had an amazing effect.

Alejandro Covalin [00:02:42]:

And I remember the doctor was waiting, for the second day or third day because it's the worst. Right? I mean, they come it rebounces.

Daniel Powell [00:02:51]:

And Instead of because, yeah, day two and three are gonna get worse and get better.

Alejandro Covalin [00:02:55]:

I remember the doctor saying-

Daniel Powell [00:02:56]:

And better.

Alejandro Covalin [00:02:57]

I was able to sit down and have a rational conversation with a person. Right. And I remember that because he was very impressed. And I remember when he said it, I can tell he was very impressed with the fact that I could have a conversation with this person on day two or day three. I don't remember if it was day two or three.

Navid Khodaparast [00:03:15]:

It was day three.

Daniel Powell [00:03:16]:

And then we saw this again and again. It was it was hard to get testimonials or somebody to talk about the fact that- but then we had the patient, Eliza, who-

Navid Khodaparast [00:03:26]:

Yeah. Eliza.

Daniel Powell [00:03:26]:

Had such a profound experience in the clinical study. She said, would you reach out to the company? I want to do a testimonial. And-

Navid Khodaparast [00:03:36]:

We weren't even planning for that.

Daniel Powell [00:03:38]:

No, No. And then she just she was so she was so mad and so didn't wanna be there and didn't wanna be part of a trial and was angry. And she says within three or four hours. She's I think she had the fast release, but by but, you know, a couple hours in, and she realized something was really different.

Daniel Powell [00:04:02]:

And went from, ‘I am not gonna continue treatment.I am gonna go get out of here and get heroin and get high’, her words, to, she finished her seven day detox and checked into long term recovery.

Daniel Powell [00:04:15]:

And, we had a follow-up a year later, and she was in a sober living home for the first time she is in her life had been sober for a year for the first time in, like, five, six years of her life have been sober that long.

Navid Khodaparast [00:04:28]:

Well, the interesting thing was, you know, when you think about someone that goes through detox over and over again, they say that cognitive fog, right, that that brain fog that they have when you take a lot of the medications that are supposed to help you, that's one of the symptoms, one of the side effects. From taking-

Alejandro Covalin [00:04:47]:

You don't feel clear in your head.

Navid Khodaparast [00:04:48]:

You're not clear headed. And so when you're not clear headed, well, you just kinda go through the steps and you're just like, okay, ‘what do I gotta do next?’

Navid Khodaparast [00:04:55]:

But for her, you know, the way I interpreted how she responded to the device was ‘I was in control of my treatment.’ Right?

Alejandro Covalin [00:05:03]:

She was she was clear-headed.I am sure that's a nice feeling for the person that they feel that they can they're clear headed. They can make decision.

Navid Khodaparast [00:05:13]:

Because we know a lot of the detox process is just kinda going through the paces. Right, you gotta go take your meds today. Tomorrow, you're gonna have a counseling session. The next day, you're gonna meet with this person, and then we're gonna talk about long-term recovery.

Daniel Powell [00:05:25]:

One of the positive effects they saw is if somebody's detoxing and they're in really bad shape, they can't make it to therapy, they're in the bed in a fetal position. Getting them into group therapy and individual therapy faster, getting their them on the road to treatment faster, a lot of people have said they appreciated that effect.

Navid Khodaparast [00:05:49]:

But those sessions also can be more productive too.

Daniel Powell [00:05:52]:

For sure.

Navid Khodaparast [00:05:53]:

Right? Imagine you're in a counseling session and you have brain fog and you're clear headed. You're clear headed. Now you can take that that feedback, that counseling, and it can be much more beneficial for you.

Daniel Powell [00:06:03]:

Yeah. So one thing I've seen, I've gone out in the field Oh, yeah. Is when we're deploying and selling and opening new centers. You go out in the field more when we're doing a clinical study and doing that.

Daniel Powell [00:06:18]:

My experience- so you almost always, like, a facility would wanna see before they believe. And so you're like, alright. Sure. Let's throw this on somebody. Like, you don't have to buy it. I'll show you how it works.

Daniel Powell [00:06:31]:

And, what's really funny is I'll I have, like, three or four times now, every time they'll bring somebody in, you're normally in a conference room and there's nurses and you serve lunch so people are coming in and out, you put this on somebody, they bring somebody in withdrawal and I mean you look at the person you're like, they are not happy, right?

Daniel Powell [00:06:53]:

When you see somebody in withdrawal, they are, I mean, they're on edge, they're in fight or flight, they're uncomfortable, if not miserable. And you put it on them, kinda explain what you're doing. Of course, it's always different because you're touching some stranger's ear. Like, may I touch your ear? And they almost always fall asleep by the one hour mark.

Daniel Powell [00:07:19]:

You're kinda looking for, how are they doing at one hour? And, you know, you're chit-chatting and having a conversation and you look over there and they're just completely out.

Navid Khodaparast [00:07:28]:

Yep.

Daniel Powell [00:07:29]:

And it's because they've been in fight or flight for days. Their brains’ not allowed them to sleep. And I, that's such a, it seems so simple, but everybody's like, ‘why are,’  you know start whispering, ‘why are these?’ you know it is-

Navid Khodaparast [00:07:43]:

Well, that's one of the side effects too, right, of addiction is insomnia. Right? That you-

Alejandro Covalin [00:07:48]:

But I guess it's because you're in fight or flight

Navid Khodaparast [00:05:53]:

You're always in fight or flight. Right? It's like imagine Yeah. You know, I had a friend of mine that was dealing with AFib and her heart kept racing at night. Right, and she couldn't sleep because of that. So imagine if you were in that same scenario but now it's for a substance use disorder. Just it's unfortunate, it's such a vicious cycle.

Daniel Powell [00:08:06]:

So I think I think we've described a couple of people we've seen in this, but one of the things we noticed early on that wasn't being addressed is there's, substance use disorder hits everybody. Every family, every demographic, every age group.

Alejandro Covalin [00:08:25]:

Right. There's no different I mean, there's no-

Navid Khodaparast [00:08:26]:

Doesn't matter how rich you are.

Daniel Powell [00:08:28]:

You go to all these websites and there's some, there's the standard guy in a hoodie in a corner. You'll you know, we've never put somebody in a hoodie in a corner on our website. We just we don't think that represents- really, I mean, the these are school teachers and-

Navid Khodaparast [00:08:47]:

Right.

Daniel Powell [00:08:48]:

Businessmen and disproportionately now with fentanyl hitting communities of color because the price point has become super low and hitting disadvantaged communities and purposefully being spread there. It is touching every aspect of society.

Navid Khodaparast [00:09:07]:

It's the most stigmatized disease, in my opinion, ever. Like, you don't look at diabetes this way. Like, when someone comes into the hospital because they have, they're diabetic, you know, we don't look at them and say, look what you did to yourself by eating bad food. We don't. We treat them.

Navid Khodaparast [00:09:23]:

We treat them kind. We treat the symptoms. We help them. We give them a treatment plan, and we you know, they go on. But when someone shows up to the emergency department with a needle stuck in their arm, we automatically assume that this person is a degenerate.

Navid Khodaparast [00:09:38]:

It's not the case. You know? It can be anyone, to your point, Dan. It really can be anyone. It can be the richest person that's a CEO of a company in Fortune one hundred. It can be someone that's just you know, that doesn't make a lot of money.

Daniel Powell [00:09:52]:

Well, in what started this whole epidemic was people getting legitimately on a pain medicine for a knee surgery or whatever, for back pain, and then developing a dependency, developing getting trapped by that dependency, until it's out of control and moves, you know.

Navid Khodaparast [00:10:12]:

Right.

Daniel Powell [00:10:13]:

Dependency is I'm gonna go through physical withdrawal and be miserable, moving into addiction as I start to use to self harm, and it's just a domino effect.

Alejandro Covalin [00:10:22]:

Yeah.

Navid Khodaparast [00:10:23]:

Well, there's severities of dependence. Right? You know, someone that just came off a back surgery just a few weeks- Just seven days, you can become dependent to an opioid, right, of just continual use, and then you go weeks, you go months, and the severity of your dependency goes up and up.

Daniel Powell [00:10:40]:

It definitely can be genetic. Right? There's those individuals that are very susceptible.

Alejandro Covalin [00:10:46]:

Why somebody gets, very rapid with the developing the dependency-

Navid Khodaparast [00:10:52]:

I think that and also the opposite. Some people when they take an opioid they have they get violently ill from it just from one pill. Yeah. Like you.

Navid Khodaparast [00:11:01]:

So that to me tells me there's some genetic component as well. Right? Why does it make someone feel euphoric, but then the other person makes them feel awful?

Daniel Powell [00:11:09]:

Yeah. I count myself lucky.

Navid Khodaparast [00:11:13]:

Unless you're in a lot of pain.

Daniel Powell [00:11:14]:

Yeah.

Alejandro Covalin [00:11:15]:

But I also think that dependency has to do with, some genetic factor where some people get the dependency developed faster.

Navid Khodaparast [00:11:25]:

Well, I think there's so many things that factor in too because when you think of just like- we're only talking about an opioid.

Alejandro Covalin [00:11:32]:

Yeah.

Navid Khodaparast [00:11:33]:

But we know our patients are not just on opioids. I I had a doctor tell me once that someone that comes in for detox, they're like a walking pharmacist. They know how much of how much heroin they need to take a day.

Navid Khodaparast [00:11:48]:

They know that that's a that's a downer. That's a sedative, so they need an upper, so how much cocaine they should take to be able to counteract the heroin so that they can just function.

Navid Khodaparast [00:11:57]:

How much benzo so you'll see patients come on on opioids, benzos, cocaine stimulants, marijuana, cigarettes, alcohol.

Daniel Powell [00:12:06]:

And now xylazine.

Navid Khodaparast [00:12:07]:

Oh, no. Xylazine is in the picture with fentanyl, and that's being spread around.

Alejandro Covalin [00:12:11]:

Yep.

Daniel Powell [00:12:11]:

Yeah. So, what are we seeing in our clinical studies? So, we've finished the FDA clinical study success on market and then had the vision of this really big long term addiction and recovery study we call RESTORE, repeating the detox portion but then adding in a long a long term recovery arm, if you would.

Navid Khodaparast [00:12:34]:

Yeah, yeah, yeah. Well, things changed a lot from that first study to second study, namely heroin was the primary drug of choice, you know, in terms of, like, street opioid use.

Navid Khodaparast [00:12:45]:

And that's more or less gone. Like, you know, the numbers come out. It's going down twenty percent down every year in terms of what's being seen. Fentanyl is now the primary opioid of use on the street.

Alejandro Covalin [00:12:58]:

Which is very unfortunate because it is much longer acting- stays in your body

Navid Khodaparast [00:13:02]:

Longer actor. It's a has a higher potency in terms of its, pain relieving effects.  It's easier to become dependent on it.

Navid Khodaparast [00:13:12]:

And so, unfortunately, someone that thinks they're taking heroin, you know, a lot of the patients we saw that we see in the RESTORE trial, they'll say, ‘Oh, I'm on heroin.’ And it is self-reported. But when you do a urine drug screen, no. You're not on heroin. You're on street fentanyl.

Daniel Powell [00:13:28]:

Yeah.

Navid Khodaparast [00:11:25]:

And so it's, you know, our first study we had eighty, I think it was eighty-seven percent, close to that, were on heroin and polysubstance use. And now the long term study, the RESTORE trial, we're looking at around the same percentage, but it's now fentanyl.

Navid Khodaparast [00:13:45]:

So, but the good thing is we're not seeing any change in terms of the treatment. So just because they're now on fentanyl, the device is able to treat the withdrawal.

Alejandro Covalin [00:13:54]:

It might take a little longer.

Navid Khodaparast [00:13:56]:

It could take a little bit longer, but I think meaning the duration of the withdrawal.

Alejandro Covalin [00:14:00]:

Right.

Daniel Powell [00:14:01]:

Well, we also changed the paradigm of the study. So in the first study-

Navid Khodaparast [00:14:05]:

Right. It was focused on treating withdrawal.

Daniel Powell [00:14:06]:

Well, the FDA had us push patients into withdrawal and then show we could bring it down. Not ideal. That's not how you wanna treat them in the world.

Daniel Powell [00:14:16]:

In the new one, we're gonna intend to prove that you could put the device on before withdrawal starts or right at the beginning, so you don't have to get uncomfortable.

Daniel Powell [00:14:25]:

We've already proven we can take away the discomfort. So, the results of that, I think, will really help us give guidance on a better way to use the system in real practice.

Navid Khodaparast [00:14:37]:

Yeah. I think if you if you talk to anyone that's in the space in terms of recovery treatment, they- the number one thing that, you know, National Institute of Drug Abuse pushes out in terms of, you know, public service announcement for addiction is harm reduction. Right?

Alejandro [00:14:54]:

Yeah.

Navid Khodaparast [00:14:55]:

Reduce harm, prevent overdose. Right? And so how do you keep how do you reduce harm? Well, you keep them in the game. You keep them in treatment. So, if the first part of the game is withdrawal, when you manage the withdrawal, okay, now they can go into long term addiction treatment, which is what the RESTORE trial is to really show.

Navid Khodaparast [00:15:16]:

We take them through inpatient detox, and then we have ninety days of outpatient, and we see if we can manage the symptoms of withdrawal, cravings, PTSD, depression, so on and so forth.

Daniel Powell [00:15:25]:

All the all the causes of relapse.

Navid Khodaparast [00:15:27]:

All the causes of relapse, and then hopefully that will prevent the relapse. If you prevent a relapse, you prevent an overdose. That's guaranteed. You can't overdose without relapsing.

Navid Khodaparast [00:15:37]:

So if we can prevent the relapse, then the patient's, you know, long term recovery is they're on the right path.

Daniel Powell [00:15:44]:

So our first clinical study, single site, recovery unplugged in Austin, and then moving to a multicenter site for the RESTORE study.

Navid Khodaparast [00:15:55]:

Yeah, for RESTORE we really, you know, we really wanted a more diverse population, right? And so, we started with the Hazleton Betty Ford. We have three locations, California and two in Minnesota.

Navid Khodaparast [00:16:11]:

And, you know, Betty Ford has a diverse population itself, but, you know, a lot of them are a little bit more high net worth, have insurance, you know, and also just kind of geographically where they are in California, Minnesota, you know, racially there's different profiles there.

Navid Khodaparast [00:16:26]:

But when we spoke with NIDA, you know, opioid use disorder is really kind of expanding across races. Right? So, you're seeing it more in African American population, more Hispanic population. It's not just in the white and Caucasians.

Navid Khodaparast [00:16:40]:

And so, what we really wanted to hit on was, can we include that in the RESTORE trial? Show racial diversity.

Navid Khodaparast [00:16:46]:

And so, we included a another treatment facility called Gaudenzia. And Gaudenzia has been around for almost seventy years.

Daniel Powell [00:16:54]:

In Baltimore, right?

Navid Khodaparast [00:16:55]:

Pennsylvania and then also in Maryland in Baltimore, Maryland. So, we have a site, just outside of Baltimore, Maryland. A location called Crownsville. And they have a more, about I think about seventy, eighty percent of that site is African American.

Navid Khodaparast [00:17:11]:

And so, we've really started diversifying the treatment to give a better understanding. Right? We cannot keep blinders on and, you know, to say that our treatment only works for this population. We really wanna show real world evidence that it can be translated to everyone.

Alejandro Covalin [00:17:26]:

And then, you have this population, the, probably the most vulnerable one.

Navid Khodaparast [00:17:35]:

What are you talking about? The the neonates?

Alejandro Covalin [00:17:37]:

The babies.

Navid Khodaparast [00:17:38]:

Yeah. The babies.

Navid Khodaparast [00:17:40]:

Well, you know, yeah, you look at the adult population, obviously, that's vulnerable population on its own. But then when you look at the babies, you know, talk about a life trajectory that you didn't ask for. Right? You know?

Daniel Powell [00:17:51]:

It's heartbreaking.

Navid Khodaparast [00:17:52]:

It's heartbreaking. And, you know, you have moms that are- and don't get me wrong. Not all moms are bad moms when you talk about NOWS.

Alejandro Covalin [00:18:00]:

No. No. They could actually have surgery, and they might be on painkillers. There's a difference.

Navid Khodaparast [00:18:06]:

Yeah. They're managing their pain, which is fine and, you know, unfortunate. But they wanna have a baby and that's great too. And, you know.  But, there's also moms in recovery that are on buprenorphine and methadone, and they're doing a good. You know, that's their- they've stayed in recovery. They've been sober. That's fantastic.

Navid Khodaparast [00:18:23]:

But then, unfortunately, there are occurrences where, you know, these are babies that are born on heroin, and I've seen I've seen some really devastating demographics.

Daniel Powell [00:18:33]:

Oh.

Alejandro Covalin [00:18:34]:

You know, it's just really bad for the Really bad for the brain when you're that young.

Daniel Powell [00:18:38]:

The list of comorbidities you've shown me, you know, babies born-

Navid Khodaparast [00:18:43]:

Oh, you know, you're talking HIV, syphilis, gonorrhea, you know, and then you list out just- It's just the laundry list is you know. It makes you really upset. So, but, I do think that when you look at that diverse that diverse population, not only from adults to babies, it's showing that the device can translate. Right? That when you have withdrawal in an adult brain because that was the first question we had. Actually, our first question really was, ‘Do they even have an auricular branch of the vagus nerve?’

Daniel Powell [00:19:14]:

Yeah, has it developed yet? Because they're normally preemies.

Navid Khodaparast [00:19:18]:

Yeah, they're premature and you know their nervous system may not have developed. And, what we found is that's not the case. They do. They actually have the neural structures available. And so-

Daniel Powell [00:19:30]:

This is the work I'm most proud of that you guys are doing.

Navid Khodaparast [00:19:34]:

Yeah, it's a really humbling spot to be in.

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