Daniel Powell and Navid Khodaparast are getting on peoples’ nerves. No, really. They’re disrupting everything you know, or think you know, about opioid use disorders and tackling the hardest part of helping people break free of the vice grip of addiction – acute withdrawal.
Spark Biomedical has developed two systems to help alleviate the worst symptoms of withdrawal. Using transcutaneous auricular neurostimulation, their wearable devices are changing lives. Check out the story behind the story in this episode of Skraps.
Hey everyone, thanks for tuning in to SKRAPS. I’m one of your hosts JoJo Platt. And as always, well except for last week I’m joined by my brother from another mother and father, Arun Sridhar. Arun was kind enough to fly solo last week while I took care of some parenting obligations. If you haven’t already done so, go take a listen to his interview with Dr. Howard Levin, you know what I’m about to ask for next, we asked for it at the beginning of every episode. But if you could take a few moments to share scraps with your friends, your colleagues, your enemies, your Amazon driver, your doordash delivery guy, we’d greatly appreciate it. Or if you’re not the sharing type, leave a review of scraps on your favourite podcast platform. It’s greatly appreciated. If you’d like to sponsor scraps or would like to suggest a guest, please feel free to stalk a rune or me on social media, we’re pretty easy to find. And with that, let’s dive into the good stuff. We’re pretty excited about this episode because it deals directly with a global epidemic. No, not COVID. The epidemic that was plaguing the world long before COVID hit. We’re talking about the opioid crisis. There are a lot of considerations in opioid use and misuse. And we’re not going to get into that today. We’re not going to get into the house or the whys. Instead, we’re going to talk to folks who are actually doing something about it. folks over at spark biomedical have come up with a novel way to ease opioid withdrawal and to make the first step in getting clean much more attainable than it has ever been. They’ll talk about their device their clinical trials and here’s a pro tip for you grab a Kleenex because when they start talking about those babies in the nick you, the tears are gonna flow. Without further ado, please welcome Daniel Powell co founder president and CEO of spark biomedical and Dr. Naveed Kota parkwest. co founder Chief Scientific Officer. Gentlemen, welcome. Thanks for coming on the show. We really appreciate having you on I know it’s even even in the face of a diminishing COVID. You guys are incredibly busy. You’ve got a new publication out this week and some great results on opioid withdrawal in neonates. Can you can you back up a little bit and tell us how you came up with the idea to use Vagus nerve stimulation for opioid withdrawal.
Dan Powell: 2:46
So there’s actually a long history of neuro stimulation for withdrawal. Naveed found papers going all the way back to 1947. In Russia, for alcohol withdrawal, they’re basically using electric shock therapy. But in recent years, there’s been a electroacupuncture. And in growing evidence for Ohp specifically for opioid withdrawal that gave us her inspiration. But I think maybe the V tells you a little when I met in the VA they were he was working on a regular neuro stem and other applications. transcutaneous Lee, so maybe you can give you some background of has has how he knew how well this would apply for opioid withdrawal.
Right. Yeah, that’s that’s great then so yeah, we were, we were definitely doing some different types of research using non invasive, irregular nerve stimulation, mainly towards cardiac disease. So for, you’re probably familiar with some of the work that came out of University of Oklahoma with several sub maracas looking at using Vegas nerve stimulation for atrial fibrillation, reduction of the burden of aphid and that was using invasive, they disturb stimulation, so the traditional stimulation of cervical Vegas nerve using a cuff electrode. But as we know, that started to evolve, you know, we started seeing this type of technology into the more non invasive setting and Steve Ross and I were actually on a grant together using VNS for A-fib (Atrial Fibrillation). And then we dabbled into using it for regular or looking at their regular approaches. Next year, we had a grant actually in Belgium, the prior company that we’re looking at how to use a regular in, in humans, specifically, that had atrial fibrillation, but that study never really got off the ground while I was there. So what we saw was that which was really important, you know, for me as a guy that had deep roots, in Vagus, our simulation for neuroplasticity, I really wanted to see if it activated certain central structures, specifically the NTS. And the literature started coming out. I think one of the earlier papers by Fred Noce pointed showing how an fMRI imaging you can activate the NTS and other central nervous region structures that are, have been associated with traditional term of VNS. And so it kind of ensued after that point.
Dan Powell: 5:33
And sort of the ironic part of this whole thing is I used to work at Cyberonics. And we had an investment in German, a regular neurological company called CerboMed. And when I got there, I heard about this as a brand new employee and I heard about this investment. I think I said, That’s ridiculous. It will never work. Who can stimulate the ear? So ironically, now I get to be co owner in a company specifically doing the thing I marked about six years ago.
Arun Sridhar: 6:00
Yeah, I actually have, it’s interesting to have how the ways of life actually worked. So I have a question for you, in terms of just explaining the science behind the vagal nerve stimulation, so let’s just take a slight detour. And we’re going to with the intention of coming back to what you’re doing at spark here. Can you just walk us through the mechanism? So just want walking through your early work at Oklahoma and and what you just described there about how the stimulation of Vegas nerve works for atrial fibrillation? Can you walk us through that mechanism in terms of what the responses were and why? And then we’ll probably kind of draw a parallel track to, from that to the mechanism here for for opiate addiction, if that’s okay,
if it’s if it’s actually better, I’d rather talk a little bit about neuroplasticity.
Arun Sridhar: 6:53
OK. Let’s actually talk about neuroplasticity
That’s Yeah, so that was actually how I drew the line from, you know, where I was coming from, from animal world preclinical Vagus nerve stimulation. So, you know, my specialty, or what I was trained to do was Vagus nerve stimulation to enhance neuroplasticity, primarily to ensure motor recovery in stroke ischemic models. And the way we were doing that was by stimulating the cervical Vegas nerve, using a cuff electrode and pairing that to motor movements to ensure that the timing of vns was paired with the timing of a successful movement. And we saw that to be extremely successful, right, we were using these are papers that are published in 2010, 2011, 2012, and so on and so forth from the Michael Kilgard’s lab and Robert Rennaker’s lab at UT Dallas. And we saw tremendous success and be able to restore motor movement in these preclinical models of stroke. They’ve taken this and translated it into other disease models, PTSD, traumatic brain injury, spinal cord injury. So some of the work that was done by Patrick ganzer. He’s now at Battelle. But the thin line, I guess, the silver lining between, you know, this invasive versus non invasive is what I described earlier regarding activation of the NTS, right. How do you tap into the central nervous system through this collaborative structure on the side of your head, right. And so there is a branch that comes off of the vagus nerve, the regular branch of the vagus nerve. And there’s some other cranial nerve branches that are nearby that we focused on. Our co founder, Alejandro Covalin, is an expert on trigeminal nerve stimulation. A lot of his background was regarding migraine pain, those types of indications. And so he had very good expertise in regard how to use transcutaneous approaches to activate trigeminal nerve branches. And I was deep into the literature on the Vegas side. But like I said, What is important was by stimulating the regular branch of the Vegas, or we do know that it has a direct projection to the NTS. And it has been it has been shown to activate the NTS. The question was for Spark. Well, how does activation NTS eventually lead to the release of endogenous opioids. And although we haven’t proven this with our own technology, there is ample evidence and pain research and an OCO withdrawl research looking at how electrical stimulation can release endogenous opioids also know that endorphins. And so we’re, we’re hedging our theoretical mechanism on that, that we’re able to stimulate this system. in a way that is beneficial, but also in a way to help mitigate the withdrawal symptoms.
Arun Sridhar: 10:07
So do you have any data that actually suggests that you’re actually able to increase the levels of, of brain or regional specific increases in in endorphins in the brain regions?
spark does not know. But there is prior literature showing how stimulation via electricity can actually increase the levels of specific endorphins. They’ve measured this in spinal, perfuse, sated CSF in animals and in humans. But that is something that spark is very much interested in and studying as we develop our mechanism of action.
Dan Powell: 10:44
And that’s one of our commitments as a company a lot of times is like, let’s keep moving the science forward and actually get this in an fMRI with our actual device, and then see that so that’s something on our radar this year, is to, you know, always be moving the science forward.JoJo: 11:05
So you your first clinical trial is with neonates, how, how did you land on neonate as a subject?
Dan Powell: 11:17
It was kind of funny. So I was flying out to the neurotech reports meeting, the neuro tech Leadership Forum meeting in San Francisco, which is where I think I met you for the first time, we just formed the company. And we were, we’re going to do this in adult. Now as long as on a flight in doing the typical market research, you know, how many, how many patients are there? What’s the prevalence of the disease? How is it you’re doing your typical business plan stuff, and I hit a link on neonatal abstinence syndrome, which is neonatal opioid withdrawal syndrome and a different name. And which I can’t remember how I streamed a video on a Southwest flight. But somehow I got the video to come through. And I saw this baby going through withdrawal, and it was shaking and screaming and crying. And it was I was just, like, so impactful. I immediately emailed an elite and Alejandro and I said, we have to make a baby device, just kind of like that, like we’re three months into the company. Just still trying to figure out what we’re gonna do. And I was like, we got to also make a baby device. I think by the time I landed, and I sent them the link, they both had replied back. Absolutely. Whether we make money off it or not. This has to be done. Like we’re the people to do it. The next day, I’m sitting in the neuro tech forum and and Bashar Badran, got up and produced and been debuted as data on neonatal irregular stem for stroke recovery and newborns. And standing before us was the only person in the world who has an IRB approval and stimulated a baby’s air. 24 hours after I saw this, I nearly tackled him coming off the stage. And I ran up to him like a crazy guy. I was like, we got to work together. like who are you? And that’s where we ended up running.
You did look a little silly. I said, you notice we didn’t really hang out very much on that conference. You did you did come off as a little aggressive.Dan Powell: 13:21
So yeah, I was just, you know, but that was, you know
it was one of those things, right. I told Dan, I was like, Well, you know, doing getting IRB is already challenging. And there’s a lot of reasons why right, especially in adult trials, you know, getting NSR for class two devices is becoming easier and easier. But going into a neonatal population, and delivering electricity is a big question mark. And I told I was like, this may be this is so admirable for spark to be able to do but without an IRB approval that we could potentially piggyback off of. It’s almost dead in the water.
Arun Sridhar: 14:05
So okay. Which which is going to be my next question, actually. Because I think therein lies the very interesting conundrum in wanting to do something to ultimately being able to do it. So I mean, just walk us through how you ensure that you were progressing from the vision or the desire to ultimately executing it, is it it only I think what I just heard you mentioned there was that it wouldn’t have been possible if you hadn’t found a clinician who already had an existing IRB approval. So just so that people can understand, can you just walk us through what the thresholds are that need that people need to overcome to be able to run a trial in the paediatric population, especially in a Natal population, then why it became easier for you to be able to do the trial with with the physician that you were Working with who already had an existing IRB approval for being able to trial, the regular regular for the stroke population or stroke withdrawal. Right?Navid: 15:09
Well, so a lot of a lot of happenstance, a lot of good fortune. I will say that you know, you, you can always push a boulder as hard as you can, but you’re going to need some luck. But when we met the Bashar, you know, that was just checking one box, essentially, because one great guy easy to work with extremely brilliant scientist. So all of those things are positives gets well gets along well with spar and our culture. His research actually was very similar to some of the research I was doing in the past at UT Dallas. So we we definitely had an intellectual commonality. But what was more important was, we needed a neonatologist right then Bashar is a neuroscientist, just like us. And being in the now is population, being able to understand not only from the neurostimulation side, but just from the physiology, and the pathology of nows. We were fortunate enough to me, Dorothea Jenkins, which is a neonatologist at MUSC, that happened to have excellent experience doing neuro stimulation, specifically through their regular branches. And so that partnership developed very quickly. And we actually discussed doing a pilot trial, because we had some small funds from Southwest paediatric devices consortium that Dan was able to get through a competition he was at. But what we knew was we didn’t have enough funds to be able to do a large enough study. So we went through the NIH pathway, right. So we we submitted an SBR with M USC as our partner, doe and I were both the P eyes on the study. And it got funded through the NIH NIH to heal initiative, and that that have literally sparked no pun intended this whole idea and allowed us to be able to do that the trial.Arun Sridhar: 17:13
But it also an interesting thing, right, you can find the neonatologist and then you you can find the person with the right experience. But they also need to have the right population for being able to do that. So I think how did how did that Nexus happen? Once you found the physician did it just so happened that she also had the the right population at hand? Or if not, that would have added another layer of complication that you would have actually had to go through?Navid: 17:42
Yeah, so. So yes, so Charleston, South Carolina actually has a fairly high population of adults experiencing opioid withdrawal, right. And then when you usually have these hot zones, hot zones, meaning during the opioid epidemic, there are hot zones, different cities, different states, if adults are experiencing high opiate withdrawal, or o UD disorder, there’s the there’s a high likelihood that the mother will also be a participant. And so yes, that MRC had a fairly high now as population. That was something we had to ensure when we put the grant and to make sure we have good enrollment for this trial. On a side note, just one thing there NOC was is actually such a good clinical site for this, they’re part of multiple knouse trials. So they’re a part of our trial. And they were also part of the eat sleep consult trial, which has, I believe, 25 or 26, clinical trial sites across the nation. And so they’re, they’re participant in several trials involving neonates.Dan Powell: 18:46
But Arun, to your point, like the process, you have to have a site and all the legal stuff to go through, you have to have the physicians and champions that know it, you have to have a protocol to get that IRB approval. And that protocol has to be well thought out. And even if that protocol gets approved, if it wasn’t a good protocol, and then you go into run the trial, you’re gonna have bad results, or you’ll discover, you know, your planning wasn’t work. So it’s an enormous amount of planning, to get to execution. And then, you know, I just was talking about to a company today that had a technology picked aside started clinical, that physicians promise the world Yeah, we can get this enrolled, they’ll tell you every time they can get an enrolled, and they never got a single patient enrolled in three years. And that could be the death of your company. And you’re like everybody said the right thing. And then there was no enrollment and, and it certainly is a challenge for our industry. I will say thank goodness, we were you know, it was serendipitous that this was our site, and our next trial is going to need multiple sites. So you know, we’re in that process of recruiting two or three more sites. To run a bigger study to get FDA approval, and it’s same challenge. And then every once you get multiple IRB is potentially and you know, you get for four different hospitals and physicians and you get 16 different opinions on what it should be. It’s,it’s fun.Arun Sridhar: 20:20
So just from a patient population perspective, so these you tried it in the neonatal population. These were the mothers addicted to prescription opioids, were they addicted to, to a kind of other kind of drug use in terms of heroin or cocaine? etc? What where exactly did the the the patient population actually come from that you tested?Navid: 20:48
Right. So I would encourage, you know, since this is published, now we have all of that data presented, and the patient demographics, and it is it’s heart wrenching to see it. Right. I’ve looked at the different it’s not just the substances that the mothers were on. It’s the the comorbidities that followed due to that substance use, you know, we had many infants that were experiencing blood borne pathogens, such as HIV, syphilis gonorrhoea than they had heart failure or heart and excuse me heart issues. That are just because it could have been that they’re preemies. And they were born too early. But yeah, mothers were on heroin, or pills. And, and benzos and alcohol. And it was, it’s awful.It’s awful. But at the same time, there are some others that had to be on these right. So they maybe they were recovering from an addiction prior, so they’re on buprenorphine or Suboxone, and they’re doing the right thing. And they’re trying to make a better life. And that’s we had several of those mothers. And on the other side, there’s just the mothers that are on heroin, right, and smoking and drinking and all of that, that just happened to have a baby and they deliver the baby.Dan Powell: 22:08
Interesting. An interesting note, best medical practice is to not get a mother to get off opioids if they’re on because withdrawal, so horrible, you could lose the baby from the traumatic withdrawal, you know, five to seven days of your body going haywire is very dangerous to the pregnancy. So best practice, let’s say a mom, mother was, you know, got pregnant, said, Look, I gotta get my life clean and protect this baby’s doing everything right, they probably are going to be on Suboxone or buprenorphine. And so the baby will still go through withdrawal. So that’s an interesting thing we’ve looked at, can we apply this to prenatal, but that if you thought a neonatal trial was hard, a prenatal trial is 10 times that, because you got two lives at risk. And I don’t, that’s another one, I throw this out to the universe, if there’s somebody out there to, you know, help us get that to the finish line to try to reduce the number of babies born, which is about 35,000 a year in the US that are born into will say born in dependency, not born addicted, because the addict is a psychological thing. But this is a physical dependence.Arun Sridhar: 23:22
So, um, your device is only used for a limited time. Correct. So it’s basically for a sub acute use for the time that they are in the hospital for I think it was, is it five days? Or is it slightly longer than that? In terms of the ways that sorry, that that’d be the?Navid: 23:40
That’s a great question or, and so the way we designed the trial was, you know, every hospital essentially has different protocols on how they deliver morphine. So morphine is the primary treatment option in terms of weaning the baby from their withdrawal symptoms, or helping the baby get through the withdrawal symptoms. And it happens to be at USC, they deliver oral morphine every three hours. And so with the idea that if you can deliver a 10, right transcutaneous or regular stimulation, and release the endogenous opioids, you may supplant the need for morphine, right. So as the baby’s getting to our three, their withdrawal symptoms are coming back up. And our two marker, we deliver 30 minutes, and we did this four times a day, right. So every every time, one hour prior to each morphia administration, we deliver 30 minutes and by doing that, our data demonstrated that we could reduce the withdrawal symptoms, which is measured on the Finnegan scale. The Finnegan determines how much morphine you need to administer to the baby. And by keeping the Finnegan number down, essentially, you would require less morphine and he would be able to wean the baby faster.JoJo: 25:02
DDid you ever have doubts about whether this would work? I mean, it seems like you guys have had a tremendous amount of luck, serendipity master planning in the skies, whatever you want to call it. But where did Where did doubts come in?Dan Powell: 25:19
all the time?Navid: 25:23
Yeah.Dan Powell: 25:25
Yeah, our first adult tramming we, we thought it should work our first adult subject, switching over that they don’t come back to the baby. So started on adults, when then why are we even doing adults did this a baby trial in the middle of it? But um, I think aveton happened on the west coast. And I mean, in we in her results, and it was our first subject. And we were up like, eight o’clock, nine o’clock at night, like where’s Alejandro, because he was running the trial. And I remember him texting, the cows score reduction. And it showed up. I mean, we knew he and I were on the phone, we’re just dying. We’re like, I hope this works. Like, what are we going to do? If it doesn’t, and that first forum came in, and we were screaming on the phone, like kids, I was jumping up and down literally on the back, I was in bed. And when the when the thing came, it was a 90% reduction in the score in two hours. And was just, you know, but yeah, we each step of the way, we don’t know. And then and then we’ve had failure. I mean, we’ve had, you know, patients leave the study one hour after starting and you’re like, you know, we’ve, it’s, it’s been serendipitous, and nothing’s been easy, at the same time.Arun Sridhar: 26:41
But it’s definitely speaks to the fact that you if you’re able to, especially for a neonate, if you are able to bring down the dose of morphine that you actually have, or the physician will have to kind of inject or, or, or give or really new in your case, as you were mentioning there, I think that is actually a significant impact that you can create, especially of all the effects that it can have on on, on the rest of the things that can happen in the developing child. as young as that I mean, that’s that’s, that’s super important.Navid: 27:16
I couldn’t agree more. And for me, you know that the data is the data, you know, you can I look at cow scores, and Finnegan scores and morphine plots a lot. But what always resonates for me is the feedback, specifically the neonates from the nurses, because they’re in it day in and day out, they see these babies constantly. And when they come and say, This is working, right, as opposed to what they’ve seen in the past, which is 1000s of babies. That’s, that resonates more than me than having a babies in a trial, one baby in a trial 100 babies in a trial. If they say this works, that, you know, it’s anecdotal, you can say whatever the what kind of data that is, but it’s impactful, because they’re, they’re the frontline.JoJo: 28:05
So I have a really good friend who adopted a baby who was born dependent on on opioids. And now this wonderful little girl is a teenager, but they’re there she will have lifelong residual effects, is there any ability for for spark or for another partner to come in and take on that follow on that, that lifelong study to see how these kids do in the long term. That’s,Dan Powell: 28:37
that’s our goal. So we see two goals here is the faster we can get. So you have an underdeveloped baby, and you’re hitting his or her liver, with narcotics, more morphine for what the current standard is 2324 days in the nick, you have this tapering. So our main, our main taper once they were on tan was about seven and a half days. So a significant reduction in the amount of morphine being administered in those early stages in life. So we do want to study this and say, okay, the faster we get them off for morphine and have all those narcotics and these very early days, it’s got to be better. And then a long term study, once we get a little bigger, a little more capable as a, an organisation to do something like that is something we definitely want to do and see if would continue neurostimulation for the first six months make a difference. I don’t know, like, what would be how would you measure that? But there’s, there’s a lot to figure out at this.Navid: 29:42
Yeah, it’s it’s a, it’s a long shot to say that that first couple of weeks delivery neurostimulation is going to reverse the nine months of receiving opioids, right. That’s, that’s a very presumptuous thought to have right. But we do know that opioids as Dan said are harmful to the newborn. They can potentially be neurotoxic. There’s studies looking at how it affects white matter, development and causes white matter damage. And so we hope that we’re able to prevent anything after they were born. Right. But whether there’s any neural behavioural changes in the six months to a minor, adolescent and teenagers, there’s a study that we would hope to partner with with someone or be able to see if our effects we are following our infants out to one year. So we are looking at that.Arun Sridhar: 30:36
Yep. Thank you. So the device for the paediatric the neonatal population received its FDA breakthrough designation just recently. And it’s also I just thought it was really cute that it is also called as a rule system, which I think a lot of the Australians given that they have kangaroo, Socceroos and many other rules in terms of how they address the various sporting teams, I think they would be extremely proud. The question then is where are you taking this now? From where from the results that you’ve had that you’ve just published? to getting the FDA breakthrough designation? What is the path forward look like? For for this particular product?Dan Powell: 31:22
Our next so we’re we’ll be looking to get a grant to help fund a bigger study. But regardless if we get it or not, we’ll we’ll move forward with a full blown study in the in the process is pretty straightforward. say that, but then it’s the FDA so. So we’ll do a pre submission meeting. And so for anybody out there listening, always do your pre submission meeting, you may not like the results, but it’s a free 90 days, FDA will answer whatever questions you have on your clinical direction, well in product direction for free. So it’s a good process. So we’ll do a pre submission, we’ll outline what we think we should do to get FDA clearance, they’ll give us the feedback. And then we’ll run a larger clinical study. And then submit it to the FDA if you know when we have the data. So and then our other thing is we have to redesign the product. So surprisingly, an ambulatory device meant to be worn on the belt for an adult really is, is an ideal for a nikkie setting. So we’re designing the earpiece different for the babies, has a loop in the front and our hand could grab it and pull it off just little things you learn from usability and all changes. So we’ll do a full revamp of the product specifically with all of our learnings for Nick you and then and then you just run the process with the FDA. I I’m hopeful on this one, there’s such a need. Also, the breakthrough, for those who don’t know, gives you a faster, more interactive response time for pre submission. So like in that same 90 day period, instead of sending answers in 90 days later, or sending questions and 90 days later getting answers, you get about two or three rounds, and they’re more interactive with FDA. So we’ll be using that process to go back and forth get agreement on the clinical study the endpoints, the powering of it, and then and then let’s just get the study done.JoJo: 33:21
So you guys have an incredibly compelling story. I mean, I think it would be an absolute breeze to pitch this to investors, where are you and your investment Ark? And and where are you going next?Dan Powell: 33:34
The last slide of every deck has a baby on it. And I’ll just leave that there while I’m pitching what we’re doing the question and answer time period. Um, yeah, there’s we have a lot of people have invested because I want to invest in something that’s really, you know, has a good mission. And, you know, not only is a good business, but you know, is, you know, hopefully going to really impact lives. So we’ve done three rounds of investment, not real big on all things considered. And we’re finishing up our fourth round right now, which is just almost full. So hopefully in a couple of weeks, I’m done. And we probably have one more to go just to get the company cashflow positive, but raising money. You know, for those starting, I heard raising money is the least of your worries. And I did not believe it. I think if you have a compelling product and a good team and plan it raising money has been not as difficult as I thought it was going to be. It’s still on it’s still a grind and a challenge and you pitch and pitch and pitch. But you know, it’s it’s gone pretty well so far. SoNavid: 34:41
Dan’s never raised money, at least not like this. But he is very good at it. So he he makes it sound like he’s monocyte it’s measured, but he he learned he learned how to do it. Anyway. Yeah, it was. It was tremendous watching him do that. And get rejected to write, how many times have you gotten rejected, so, but yeah, you can do those those bumps and grinds, he made it look, you know, easy, which was incredible it is it is nice to have an opioid epidemic behind you though, right? As bad as that is to say that it’s true. And it’s, it’s something that, you know, we’re passionate because there is an epidemic and we want to make a change to it. But people everybody knows about it. So the story is there.JoJo: 35:30
And now that COVID is finally wrapping up, and it’s going to be over and gone. So I can get back on the plane. And we’re going to be able to focus back on the first epidemic, and, and the opioid epidemic. And I can tell you here in San Francisco, I can’t drive from my office to my house, which is four miles without seeing at least three drug deals, and half a dozen people sprawled out on the sidewalk, just riding in either the highs or the lows of their addictions, oh, it’s,Dan Powell: 36:00
it’s horrible. And it is through the roof because of the pandemic. So what we think we’re gonna see is about a 40% increase in overdose deaths and 2024 in, you take somebody somebody’s dealing with addiction, and the primary aspects of their life that can help recovery is meaningful employment, surrounded by family, positive, hopeful outlook. And those three things got destroyed by the pandemic, you lose your job, you’re isolated at your home, and the world burning down around you. And death tolls are clipping up on the TV every day. It is horrible for the mental health field, and it’s depressions up, suicides up and addiction. relapse is just through the roof. It’s really a tough scene behind how awful the pandemic is, in all the lives that’s taken, it’s hard for it to get noticed. But our our behavioural health physician partners at the beginning of COVID, they’re all panic because they don’t have any business. And then about three months in, they’re overwhelmed with spousal problems, depression, everything under the sun. So it’s, it’s definitely taken up, there’s a hidden a hidden damage that’s not being calculated.Arun Sridhar: 37:25
So can you actually give us so you painted a picture of what the neonatal product root product look like, look like now? Like moving from there to the to the vision of the adult version of the product here? Can you tell us a bit more about what the intended use cases for the for the adult population? Where are you targeting? Can you share a bit more about that?Dan Powell: 37:54
Yeah, um, so when we began the company, we were first focused on acute withdrawal. So the five to seven days of trying to detox from substances such as heroin, and we that was sort of our beachhead, where we began It was kind of kept the clinical trial down rather short. And in the predicate devices, the electroacupuncture devices that are out there, gave us some some guidelines that are, you know, it’s, it gave us parameters to study and compare against and to get our FDA clearance. The vision always was though, then to expand this product out beyond that. So after you go through an acute detox, you still have, you still feel horrible. And your brain has been altered functionally and structurally from years of being bathed in opioids, and the basic so the body I would say, the body’s lazy. You give it a chemical, it stops producing it. bodybuilder takes steroids, they stopped producing testosterone. And then when they stopped the steroids, they don’t automatically start back the body’s asleep. Our hypothesis is that’s the same for the brain. And that is it does it does it produce its own endogenous endorphins? And then you remove the exogamous, endorphins. And you’re left with a brain that is in a deficit, to deal with stressors to deal with panic, your fight or flight sense. Everything is broken. I have a family member that’s a heroin addict, and you just tell he can’t. When he’s clean, he can’t handle life stressors. And this is a real problem for recovery. So our next step is to then extend the therapy for the next 6090 or 180 days. We’re figuring that out, study that and see if we can prove recovery and help restore the brain to some degree back to where it can produce its own endorphins and handle the stressor.Arun Sridhar: 39:53
So that’sspecifically talking about prescription opioid addiction. Correct. You’re not talking about heroin or cocaine or heroin, or any opiate, any of them that you’re talking about. Okay. All right.Dan Powell: 40:06
Most of our adult subjects were on, what’s it like? 1200 morphine. milligramme equivalents, so about a gramme of, of heroin a day. Also, a lot of them are detoxing from alcohol, and or methamphetamines as well. So, yeah, so we’re talking prescription, or four out of five people using heroin, originally started on pills, lost access to the pills, were going through horrible withdrawal in move to heroin. And thisNavid: 40:36
and this, again, this was abrupt discontinuation, right. So they took what they call an addiction world, their Hurrah dose, the night before they check into treatment facility. And then the next morning, they start experiencing withdrawals, it’s usually about 1224 hours, right? But for heroin specifically. And then they start the trial, if they if they’re still in the right mindset, some of them don’t consent, right? Because they think, Oh, this sounds great, I’ll try this new, this new device, it sounds like it will work. And then that’s when they’re still under the influence. And then when they start coming off experiencing withdrawal, it’s not their first rodeo, you know, they’ve a lot of them go through rehab multiple times, and they know what works. So trying something new that might not help them in withdrawal, which, by the way, they feel like they’re going to die in this setting. It’s It’s scary. And so yeah, it’s the fact that the device showed an effect that it did. And you know, the first one hour in my mind you they had no even no comfort medication during that first hour, it was just the device. And then we allowed comfort medications throughout the rest of the trial, but no opioids,Arun Sridhar: 41:52
which is exactly where I was going to go, because in terms of the endpoints, just to contrast this with a with a neonatal study there, you were actually looking at the reduction in the dose of morphine that would be administered to the to the child, whereas here, you’re actually looking at when they are people are checking in to kind of kind of D addiction centres, etc. They don’t have or technically they shouldn’t have any access to, to kind of opioids, then in that situation, you’re actually trying to use the device to minimise the symptoms of opiate withdrawal. And therefore, it will be a combination of both physician reported as well as subjective kind of endpoints, etc. Is that is that the right way to put it?Navid: 42:36
That’s exactly right. And so in the adult, yes, there’s no opioids, you know, obviously, they’re monitored, and they’re sure that they’re not bringing anything from the outside of the facility. But yes, there’s no opioids. You know, we’re constantly doing urine drug screens. And then even at the end of the trial, we did what was called an alloxan challenge, which is a way to determine physiologically if they’re 100% detoxify. So if they have any residue of an opioid brain, they’ll go into what is called precipitated withdrawal. And that is a determinant that they’re not fully detoxified. Some some patients on shorter acting opioids like heroin can get through that much quicker five days is typically enough for full detox. But then if you’re on longer acting opioids, such as methadone and some of the other buprenorphine types, it can take seven to 10 days for acute detoxification, which is something that we’re looking into as well past the acute phase into the protracted withdrawal phases, which happens on you know, this, the ensuing weeks or the following weeks post acute detox regarding the VNA. That is, that’s actually something that we’ve that data has been very influential for us, specifically in the pain population, because that’s more of a traditional tapering idea. They’re on an opioid. And we’re just essentially weaning them or tapering them down to a desired dose and the neonates, the desired dose is completely off. For adults, that may be Oh, I may be too high, I might be 120 me DD per day. And I need to get down to the CDC standards of 50 m add, or I need to move on to a pain pump as an alternative treatment measure. So I need to be off the opioid not only in a certain amount of time, but then also stay off for a period of time before I can go on to another intervention. So yeah, you’re painting the picture correct.Dan Powell: 44:34
In one interesting note, back to our original clinical trial, we had to have the patients in moderate withdrawal, so that we could show we had a reduction and withdraw. So we were waiting to the patients like we had to wait until it kind of felt pretty bad. And then show the effect of the device. Our next study, we’re going to be able to administrator that. I mean, ideally, why would you like what if we could just prevent withdrawal all together? It’s like this for the FDA we had to show we could bring withdrawal down even though you would know 100% of people will go through withdrawal, they stop using heroin, but we haven’t made them go up and then show they would come down our next study, because we’ve proven that we just let them put it on in the beginning, and hope they never go above I very mild withdrawal the entire time. And that without being more humane, and, you know, a more ideal path for patients.JoJo: 45:27
So you have you have the data, and you’ve obviously published on this, which will include the the publication in the show notes, but a lot of those are based on scores, especially in the neonates, where they’re nonverbal Of course, what are some of the in your adult trial? What are some of the anecdotal? Have you heard anything back from the patient’s? I mean, as you said, and this isn’t their first rodeo, so they’ve got to have some comparison? Were they able to share any of that with you?Navid: 45:56
Oh, absolutely. Yeah, we have a lot of anecdotal patient testimonials. You know, it’s on our website we have video of it is on our website, we have a video of one of our patients in the trial that you describe Jojo. Yeah, not her first rodeo was very reluctant to even be in detox, has tried, even orphan has tried many different types of medications to treat her opioid use disorder. And, you know, one patient even said it was the easiest detox ever, which is really weird to hear, you know. So we had all sorts of different types of patients. And yes, they all provided their feedback. And it was positive, right? It was definitely it wasn’t. It wasn’t like, they were saying, Oh, this made my detox worse or anything like that. It was it was all on the side of this helped me and I would I would, I would one thing I’m gonna say real quick. They talk to each other too, right? So it’s, it’s kind of an inpatient detox facility. It’s, it’s a residential treatment facility. So it’s like a home, right? And so there’s multiple rooms, there’s kitchens, there’s, they sit outside and talk to me. And recovery on blood was where we administered the trial. And they have a lot of music type treatments, it’s Kumbaya type setting. And when they see one patient with an earpiece on and they’re like, Hey, what’s that? And like, I’m in a clinical trial. And you know, I’m getting treating me, well, how come I can’t get that, you know, and so, then word starts creating a buzz amongst the treatment facility. It’s, it’s an it’s a fascinating environment.Dan Powell: 47:37
We have one patient, one of our early patients, I think, is number two or three, went through the trial, did great. relapse fell off the waggon a couple weeks later, used again, wanted to get back in and came back and was like, Can I get back in that trial and we can’t re enrol the person in the trial, we’re trying to figure out what to do. But that was a, you know, I think that was a good testament like, hey, that thing got me through this helped me get back on right back on the path soJoJo: 48:06
so I have the unfortunate experience of being right next to people as they detox from heroin and meth, alcohol, any combination of those things and you know, in that and I know that living environment that’s very close and communal and part of the process and maybe one of you can do this because I know I can’t without choking up Can you tell us some of the things that somebody going through detox go through? What’s that experience because I don’t know that people fully understand and appreciate the brutality of it.Navid: 48:45
Then you explain that play better and I can’tDan Powell: 48:48
everyone will tell you they think they’re gonna die. And not like I think like, they believe they are going to die. The amygdala is completely malfunctioning, where you process fight or flight. So besides the, the physiological things which you can talk about, you’re in a state of absolute sheer fight or flight, I’m gonna die panic that you’re trying to will yourself through with logic, and it just can’t be done. I mean, that’s, that is why this is such a diabolical drug. Math is bad cocaine’s bad smokings bad for Yes. The amount that putting your to get off. opioids put you in a state of of irrational thought, which is why when people are going through withdrawal, they will say anything they will do anything they will steal they will harm their loved ones because it’s that or die in their in their in their brain. And then on top of that, I watched one video UK guy and he said it was like his bones were boiling one minute and freezing. The next was such the pain. Remember, we go back to the amygdala, also process As pain signals, and when it’s dysfunctional, you’re feeling pain worse than you should. So you’re miserable. Your your guts are completely cramping and you’re running to the bathroom constantly. So you don’t always make it. So it’s embarrassing. sweating. Interesting, what’s not you just snot like because your, your sympathetic nervous systems just completely blown out. And so just tearing up snotting everywhere, sweating through your clothes, it’s horrible. And I, I’ve learned that I’ve I my position has changed as an opinion on this political or whatnot that I just think we treat people who are addicted so poorly. And what they just need the just, if we can have more humanity for how tough it is like, okay, you messed up, and now you’re trapped. And it’s gonna take several rounds of detox of rehab or whatever to get through it. But you know, just, it’s just miserable. It’s just hell, and so they have to go through hell to start to get better. And then once you’re through detox, which is miserable, you still feel horrible. your bones ache, you’re producing endorphins, which helps regulate pain, anxiety, all that. And then you have to also deal with all the bad choices, and that just enough to make somebody go, this isn’t worth it. And I’ll just use again, because, you know, just because you’re detox doesn’t mean you fix the underlying challenges. Yeah, we’re really rough on our, our citizens on how they’re treated.Arun Sridhar: 51:38
Yeah. Unfortunately. So a couple of questions, which I will edit it in, which I should have meant to ask a few minutes ago, in terms of the clinical trial and the adults, is that or, or for that matter, even in the neonatal population, where they placebo control? Or did you have parameters that were ineffective that you tried? Or did all patients get the therapeutic levels of stimulation? In the trial? Yeah, so or did you have any type of RCT design where patients actually came off in certain ones, etc?Navid: 52:11
Right, so I’ll start with the neonate. Since it’s published, that was a phase one trial that we got funded through nyda. So it was an open label trial, everyone had okay saying that you does it make neonates, you know, they don’t, there’s no bias to interventions per se, right. In the placebo side, it could be that they’re in there, they’re in a clinical trials that are getting more attention. And that could influence their direction of how they recover. And we not morphine, but national averages and national averages. And you can even go by hospital by hospital, if you look at just m USC we represent that data in the study. But it was a significant shift of the amount of days from what the mo C’s historical data looked at, in terms of morphia. And so No, it was not a placebo controlled trial. In the adults, again, you design studies for a number of reasons. In the case of the adult spark was young, we didn’t have a lot of money. So we weren’t able to do huge big trials, nor that we need to because we were predicating off prior technology, going through the 510 k pathway. That predicate study was retrospective, and, you know, open label. But what I would say is ARB so we designed the trial to be almost a crossover design in some way. It’s we had to keep in mind ethics involving the patients, meaning that we have two groups, one started active stem, the other one had no stimulation. And then after 30 minutes, the no stimulation group then started to receive active therapy. So there was a very short window of time that we could compare across the active versus no stimulation. There was a lot of debate when we designed this trial, mainly from the physician standpoint on with a patient bear two hours, three hours, six hours one day of no stimulation before they say Nope, I’m out, give me give an orphan or give me some other type of treatment. And that was a that was a question that we had to decide almost from a business standpoint, as opposed to a clinical design because it would have destroyed our enrollment and potentially drawn out our FDA clearance time, which then require more funding and funding and funding. So we had to be very delicate on how we designed the trial. We tried to put the best randomised control trial we could for what we had. And as Dan already stated, this is just the beginning. You know, the the next clinical trials are not hinged on FDA, or money. It’s based on how do we prove that our technology is providing the therapy that we negatives.Arun Sridhar: 55:02
Fantastic. That’s great. So and then one final question for me here, which is, who pays for the devices? So is it the patient themselves? I assume? Or is it the healthcare system, which in the case of opiate addiction, depending on what it is, etc, it may or may not cover that. So can you just tell us a bit more on what you are thinking about the future commercialization model here.Dan Powell: 55:31
So, for the adult device were 60, about 67 days into FDA approval, so we started selling, there is no reimbursement when you’re novel and new, this is the challenge you face, the beauty of it being a wearable, at least you’re not paying for an implant, or there’s no surgery or procedure. But it is patient out of pocket pay. And we’re working through early centres, taking our time working through business models with the doctors how to make this as affordable as possible, while still having a healthy business. Physicians do basically buy it and resell it. So you can think of it as if you went to a doctor that did stem cell therapy, it’s not reimbursed, but they administer it, and you pay them. And we have like a credit system where the patient can get a credit card on the spot with 15 months, no interest to cover it, trying to make it as accessible as possible.JoJo: 56:28
That’s a great model, I mean, that a lot of what you were talking about some of the reasons people become dependent in the first places is traumatic events, or life altering events. And that includes financial reasons. So I think that’s a, it’s a beautiful offering. And I think one that, you know, I can easily see a charitable use support. For something like this, it makes a lot of sense. It’s what we’re trying to partner, find good partners for exactly that.Dan Powell: 56:57
Unfortunately, no matter how much money This saves the system, and how great and how, obviously, it’s worth reimbursement, it’s just going to take us a couple years, and just you just can’t, as a small can, you know, if we were Medtronic, you can make things happen as a small company, you know, with our resources, just reimbursement as a process, we’re just going to have to, to go through even it’s Medtronic and even better, Boston can’t make it go that much faster. But you know, we’re even, you know, smaller and less influential. SoJoJo: 57:28
for now,Dan Powell: 57:31
just today,JoJo: 57:32
and it is one of those altruistic things where you’re like, Okay, we’ve demonstrated its work. Now it works. Now the world needs to step in and do the right thing and get this to the people who need it. So I wish you guys great, great success, and really rapid luck with that one. So So what’s next for spark?Dan Powell: 57:52
Oh, so we have long a long term addiction study that we’re looking at starting this year. And that’s studying, can we help them the curve of addiction recovery? Like, can we help people stay clean after we help them detox? Were those. So that’s big. And then the big baby study this year to an image a brain imaging study, we for a small company, the list of clinics, clinical activities for nivi this year, more than ever even did a big fortune 500. SoNavid: 58:31
yeah, we definitely are pushing all cylinders on clinical and research, you know, and publish. We want to keep publishing, you know, so, you know, we published it’s ironic that we started the adult trial first and completed it actually first. But you know, going to the FDA that data gets kind of just sits until it’s through the FDA. Put on them really? Yeah, you put it on ice and then the neonatal trial caught up and completed. And so we republished first and then neonatal. But yes, the adult trial is being we’re almost done with that, finalising the data analysis and we’ll publish it, hopefully very soon. I think everybody will appreciate it.Dan Powell: 59:17
We have a white paper on the interim analysis of the adult. That’s a thing available on our web or you can click to request and it’ll be sent to you. And then we finished the some more patients and that’s what’s being compiled for publicationArun Sridhar: 59:35
right plans to move into Europe or is it strictly staying us focused company?Unknown: 59:40
We’re getting our ISO compliance audits this year, so that we can get to Europe. On top of everything and then we’re also have a redesign. We have to redesign so the product coming so we’ve learned a tonne. We’re testing some different configurations. something silly like the electrode sits right on the hair. line. So we people have to shave their hair if they don’t have short hair like myself. And that’s a barrier to entry. You know, it’s just so we’re moving the electrons around slightly to try to get off the hair lines and silly things like that though, but it’s just iterative, to continue to improve the product and make it as easy as possible to to use so I thankJoJo: 1:00:23
you guys so much for coming on and really appreciate it and like I said, best success and luck to you guys and quickly to please.Unknown: 1:00:33
Thank you so much. Thanks so much genuine pleasure.Navid: 1:00:36
Yeah, absolutely.Arun Sridhar: 1:00:43
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