Navid Khodaparast [00:00:01]:

Have you ever been curious about what happens behind the scenes at a medical device company? Do you want to take a journey with us? From a scientific discovery to an FDA cleared product? I'm doctor Navid Khodaparast, chief science officer at Spark Biomedical. Joining me are my co-founders, Daniel Powell, CEO, and doctor Alejandra Covalin, chief technology officer. Welcome to spark a conversation.

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Daniel Powell [00:00:25]:

So, Navid, when you were starting your career, did you ever imagine being. Being here?

Navid Khodaparast [00:00:30]:

No. No, I never thought I'd be a founder of a company. I thought I'd be doing science, and I thought I'd be running clinical trials, but not at this level.

Daniel Powell [00:00:37]:

Like in a academia lab environment.

Navid Khodaparast [00:00:40]:

No, I didn't want to be in academia. I think doing my grad school work and then postdoc, and then I had a clear line shot to industry, because there's nothing wrong with academia. But being a professor and living that life, for me was not the option I saw better at. I saw better options of helping patients in the industry. No, the first studies were essentially looking at how to help use vagus nerve stimulation for stroke recovery. So this is where you would implant the cuff. So it's an invasive procedure. Alejandro knows this very well.

Navid Khodaparast [00:01:10]:

And then you would retrain them. The patient would be experiencing an inability to move their hand. And so every time they would try to grasp something, we would deliver a little bit of vagus nerve stimulation that would then tell the brain that the hand is trying to move, and we rewire it, and it would regain function over weeks and months. This was pretty remarkable. Nobody was using vagus nerve stimulation.

Alejandro Covalin [00:01:32]:

And that goes through. The cognitive aspect of.

Navid Khodaparast [00:01:36]:

It does.

Alejandro Covalin [00:01:37]:

Because it's helping you with rewiring.

Navid Khodaparast [00:01:41]:

Well, if you think of just rewiring, what that means it's creating another memory. Right. So the cognitive aspect is what Alejandra is talking towards ISDev by releasing these neural chemicals like norepinephrine, acetylcholine, serotonin. These are chemicals that help the brain create new memories. But in this case, the new memory is how to move your hand again, because.

Alejandro Covalin [00:02:04]:

And I think it's important because when they have a stroke, the circuit in the brain that used to make that movement is gone. So they need to make a new one.

Navid Khodaparast [00:02:15]:

Yeah. I always look at the brain as real estate. So if you have an area that's just. There was a. Let's say there was a farm there, and it got burned down. Those are all the neurons that left? Well, there's farmland next to it, so can I just plant my crops there and regain my farm? The answer is yes.

Daniel Powell [00:02:34]:

That's fascinating.

Navid Khodaparast [00:02:35]:

So if you think about it from that perspective, the brain is just an infinite area of a network that you can just keep retraining and gain new function or lose function.

Daniel Powell [00:02:44]:

Fascinating.

Alejandro Covalin [00:02:45]:

And then you did some TBI stuff.

Navid Khodaparast [00:02:47]:

A traumatic brain did some TBI work. Yeah, we were looking at how to, again, regain function, but also looking at some of the inflammatory components.

Alejandro Covalin [00:02:57]:

Right. That's the worst. When they get stroke, too. Stroke, you also get the inflammation.

Navid Khodaparast [00:03:02]:

Right.

Alejandro Covalin [00:03:03]:

But TBI, you get more tv, you get more.

Navid Khodaparast [00:03:05]:

Well, it depends on how severe it was, obviously. But I think for, again, there's always a level of where the injury happens and then what the outcome of the injury is. But if you look at it from a preventative standpoint. So let's say you have a stroke or you have a TBI and you hit your head, those neurons, those brain cells, they're essentially inflamed and they're on the verge of dying. So can you prevent them from dying?

Daniel Powell [00:03:33]:

Can you stop them, remove the inflammation?

Navid Khodaparast [00:03:35]:

Remove the inflammation, save the brain cells, and then preserve the function. Right. And that was actually some. That stuff kind of led me in the spark, too, because that's when I learned about the Feinstein Institute and what they were doing in terms of using vagus nerve stimulation to reduce inflammation. But they were always talking about, like, arthritis, and they were talking about Crohn's disease.

Alejandro Covalin [00:03:59]:

Right. They were not talking about.

Navid Khodaparast [00:04:00]:

They weren't talking about the brain of. And so when you look at it from that perspective, you could say, well, can we use it to help heal the brain? But then, do you need a cuff? Do you need an implant to do it? And so that's when it eventually started evolving into, we can do this non invasively, which is exactly what we did at spark.

Alejandro Covalin [00:04:20]:

Yeah.

Daniel Powell [00:04:21]:

And then we've taken that idea of healing the brain, healing a stroke brain, but to healing a brain, an addicted brain that is malfunction, has malfunctioning components, which is why I really do believe addiction is a disease. It is a malfunctioned organ, and it is not a willpower thing.

Alejandro Covalin [00:04:44]:

Well, it is maladapting. Probably the best.

Navid Khodaparast [00:04:47]:

Well, it hijacked, basically.

Daniel Powell [00:04:49]:

Yeah.

Alejandro Covalin [00:04:51]:

You rewire, they change the gains in the connections. And now they're making decisions differently than you and I. We don't have that dependency.

Navid Khodaparast [00:05:04]:

I look at, like, the substances, they essentially, when it hijack, it just hijack the most primitive sense you have. Right. Which is reward.

Alejandro Covalin [00:05:14]:

And the fear.

Navid Khodaparast [00:05:15]:

And the fear, you know, if you take over reward, you're in a really bad place. Right. Because you lose sense of what you need to survive.

Daniel Powell [00:05:27]:

Yeah. You reprioritize everything.

Navid Khodaparast [00:05:29]:

You reprioritize everything. And so. And unfortunately, that is a very tough challenge to be able to reverse.

Daniel Powell [00:05:39]:

So, Navid, you spend a lot of time thinking about clinical trials, clinical trial design. Kind of give us the background. Like, what were you thinking on the first trial?

Navid Khodaparast [00:05:50]:

Oh, well, the first trial was, to me again, it was just, you know, I always talked a lot with Alejandro about it. I was like, the science is going to work. I was like, just, I had no question. The science was. Was plausible and acceptable, and we're going to see an effect. It was, can we design the study in a way that one showed it was safe, two showed it efficacious, and then showed that big drop that you wanted to see. You know, your eyes were so big when you saw Parkinson patients, their hands would stop shaking. Can we see that same effect and withdrawal? So how do we capture that but then also plant a few seeds so that when we finish the study, we have another indication we can go after.

Navid Khodaparast [00:06:29]:

We can go look at PTSD, we can go look at depression, we can look at cravings. And so we really wanted to, like, hit that hard in that first study because it was the first one. That was it.

Alejandro Covalin [00:06:38]:

Yeah. Seeing that biggest, big change was the main, you know, it was to some, before we started, it was like, are we going to see this very quickly? Like this? Can you see this effect right away?

Navid Khodaparast [00:06:56]:

Right.

Daniel Powell [00:06:57]:

Our goal was 15, one 5% reduction, and we saw 550. So it was significantly exceeded expectations.

Alejandro Covalin [00:07:07]:

But the amazing thing was that you could actually see the change very quickly.

Navid Khodaparast [00:07:13]:

Well, you didn't just see it in the score, the cow score. You saw it in the patient. The patient was clearly from when they were just in the fetal position, and they're trembling and they're sweating and they're running to the bathroom, they're pacing around, and they're just pure anxiety. And then 60 minutes, 2 hours later, they're just, you know, either they fell asleep. Either they fell asleep or they were essentially just having a conversation.

Alejandro Covalin [00:07:40]:

Yeah, but they respond quick, right? I mean, yes. To see a very dramatic change, you wait an hour, 2 hours, but in some cases, you'll see it, they calm down.

Navid Khodaparast [00:07:53]:

But this was eye opening for me because, you know, with the prior work.

Daniel Powell [00:07:58]:

With Vegas nerve stimulation, and then we took that and we always had a vision for long term addiction. Like, if we can help you in acute withdrawal, can we addressing withdrawal is important. That's the barrier to recovery. But can we actually bend the curve of recovery? I think was what we used to say in the early days. Can we really impact the opioid epidemic materially?

Navid Khodaparast [00:08:22]:

Well, yeah, I think withdrawal is the barrier, but at the end of the day, that's nothing making a huge change in terms of addiction recovery. Right. Meaning what the numbers show in the US are overdose and relapse, and that's long term issues. So we knew if we could get the patient through withdrawal, and then they could have a fighting chance for long term recovery. So by looking at depression and PTSD, these are usually the masquerading symptoms of addiction. Yeah.

Alejandro Covalin [00:08:53]:

And I think I. And we discuss this many times, but I think that addiction, once you have the dependency, it becomes a kind of a cognitive problem. You need to relearn not to be dependent at a neurological level.

Navid Khodaparast [00:09:13]:

Right.

Daniel Powell [00:09:14]:

Yes.

Alejandro Covalin [00:09:16]:

I think that's also where we can help.

Daniel Powell [00:09:19]:

That's our underlying theory of what we're doing in this long term recovery clinical trial, is that can we retrain the brain to produce its own endorphins, manage its own stressors, do the functions that it was dependent on the chemical to perform for it? And we used your background in neuroplasticity and stroke recovery, brain retraining and relearning a lost function, and applied that concept to this long term addiction study. So that's been three years in the making. These things are not fast.

Navid Khodaparast [00:09:59]:

Yeah, the restore study has been a journey, to say the least. We're almost done with it, thankfully. But the idea is, just as you stated, it's retraining the brain. You know, you got. If you keep the patient or the. You know, this. Unfortunately, someone is suffering from opioid use disorder, and you keep addressing and showing them positive feedback by saying, okay, you've crossed this barrier. You don't have withdrawals anymore.

Navid Khodaparast [00:10:22]:

Now you're able to reduce your cravings. Now your PTSD is coming down. Now you're having a better outlook at life. These are all positive moments that are getting reinforced in the brain, and then there's recircuitry that's occurring.

Daniel Powell [00:10:36]:

So you're retraining the brain that the stimulation is causing.

Navid Khodaparast [00:10:39]:

The stimulation is an Aidan. Yeah. It's actually helping them get through.

Alejandro Covalin [00:10:43]:

It's helping. The stimulation is enabling, is helping. But those positive outcomes reinforce the neurological change. The device, the stimulation, helps make those changes easier. Yeah, because you're triggering the mechanism. You're triggering.

Navid Khodaparast [00:11:01]:

Well, if you think of it just from mechanism, from just vagus nerve simulation. Right. You know this very well. It's just. It's an arousal signal, right? So when the brain pays attention to something like PTSD, these are arousal events. Right. When you have a really traumatic event that's a memory that's being formed and essentially is traumatic, and it's hard for the brain to ignore it, we're essentially doing the other thing, the other way around.

Daniel Powell [00:11:25]:

Well, and I think that perfectly leads into our newest work we're starting, and that is with acute stress reaction trauma, treating the traumatic event. Right. When it happens in the emergency room on the battlefield, that creates the PTSD that causes the substance use disorder. So we've started to go upstream to the cause of the event that triggers this cascade that ends up in addiction. And that's really, I think, big picture. What our commitment has always been as a company is that we are going to give back to the science. We're not one and done. It wasn't just get our FDA indication for withdrawal and finish.

Navid Khodaparast [00:12:11]:

There you go.

Daniel Powell [00:12:12]:

And just keep selling that. We want to unravel this whole problem end to end, and we're making progress. It is not fast or easy at all. No.

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