The NOWS Story

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 Dr. Navid Khodaparast, Chief Science Officer at Spark Biomedical. Joining me are my co-founders, Daniel Powell, CEO, and Dr. Alejandro Covalin, Chief Technology Officer. Welcome to Spark A Conversation.

Daniel Powell [00:00:24]:
I think we get the question, like what really motivates you? And it has to be our work with neonatals. It is just, it's a passion project of ours. And so, babies who have been exposed to—newborns who have been exposed to opioids in utero during a pregnancy can be born with something called neonatal opioid withdrawal syndrome. So, I mean, the treatment is very slow and archaic.

Alejandro Covalin [00:00:56]:
Not only that, the treatment is with opiates. They give morphine to the babies and that's unfortunate, but that's what they do.

Navid Khodaparast [00:01:06]:
Well, they start, they try to console them and they essentially give them the option of non-pharmacological approach.

Daniel Powell [00:01:14]:
And that's new.

Navid Khodaparast [00:01:16]:
Not all babies will withdraw, right? So only usually about, I think it's roughly about 50% of newborns that are exposed to opiates in utero will actually withdraw. So, most of them will just be, you know, they'll have very mild withdrawal and that doesn't require them to go on pharmacological treatment. But of the ones that do require it, yeah, Alejandro, you're right. They go on to oral morphine replacement treatment. But then in some cases, if that's not enough, they'll give them phenobarbital, clonidine. So just more medications for an infant that's typically premature.

Daniel Powell [00:01:55]:
These babies are premature, underweight, often have devastating comorbidities such as STDs, breathing problems, neurological deficit and delayed development.

Navid Khodaparast [00:02:14]:
That lead to lifelong consequences. If you look at some of the NOWS studies, you'll see, obviously you'll look at the first year of life, but then you can also look at long term, adolescent to teenage years. And, you know, they're having delay in terms of cognitive performance in school, they're having social interaction issues with their friends, they have ADHD, they have some cases, their higher propensity of depression and anxiety. It's all because, you know, that first interaction with an opioid and how it changed the brain going forward.

Daniel Powell [00:02:48]:
So, we, you know, this wasn't even on our radar when we first started. We didn't even know it existed.

Navid Khodaparast [00:02:53]:
We didn't know it at all.

Daniel Powell [00:02:55]:
And I ran across it while doing market research to build an investor deck. And we all pretty much immediately agreed over email that we have to work on this and then begin the process of how do we do it? What was the biggest technical challenge? Probably making the miniatures, making electrodes smaller.

Alejandro Covalin [00:03:16]:
Well, there were two. The first device we made was not intended for babies. And what I meant by that is we were not thinking about people using the lowest intensity, things like that. So that was a big challenge because we had to retrofit the devices to allow us to be accurate at very low intensities.

Daniel Powell [00:03:44]:
Yeah, that's right. Because we were kind of inaccurate in that 0 to 1. Because we said, who cares 1 milliamp if you're not accurate?

Navid Khodaparast [00:03:51]:
Most people are going to go well above that in adults.

Alejandro Covalin [00:03:54]:
So that was one challenge. And then, of course, the morphology of the ear of the babies. Some of them are not fully developed, the actual shape. And so the electrodes. We had to figure out a way to make the electrodes to fit the babies.

Navid Khodaparast [00:04:08]:
And then you think about the behavior of the baby too, right? They grab everything. So in the adults, you know, we always have the tail end going down the front, but with the babies, we would always put the tail behind them. It would go down the onesie and then come out the back, and then it would connect to the controller. So that way we'd prevent them from grabbing and pulling the earpiece off.

Daniel Powell [00:04:29]:
Yeah. What was your biggest concern going in from a clinical standpoint?

Navid Khodaparast [00:04:34]:
One, babies—they don't talk. So how do you know? A lot of the reporting that we do in the adult trials is patient-reported: “I feel this way,” or “I feel it,” or “I don’t feel it.”

Alejandro Covalin [00:04:50]:
Or uncomfortable, or whatever.

Navid Khodaparast [00:04:52]:
With the neonates, you're going off almost instinctual feedback. If the intensity is too high, we would look for face grimacing, squinting—signs of discomfort. That’s how we knew to turn it down.

Navid Khodaparast [00:05:06]:
But that was one concern. And two—the good thing in the NICU, the neonatal intensive care unit, is there's a good assessment of withdrawal. They have what’s called the Finnegan Scale, which is actually much more comprehensive than the adult version.

Daniel Powell [00:05:29]:
Which you would hope so.

Navid Khodaparast [00:05:30]:
Exactly. Especially in an ICU, you'd want something very comprehensive.

Alejandro Covalin [00:05:35]:
Well, if you cannot ask the patient how they feel, you have to have something.

Navid Khodaparast [00:05:40]:
You have to have something.

Alejandro Covalin [00:05:42]:
Yeah.

Daniel Powell [00:05:43]:
So, this rolled into our first proof of concept. We adapted the product, made the protocol, and got a great clinical partner with MUSC, the Medical University of South Carolina.

Navid Khodaparast [00:05:56]:
Yeah, we partnered with pioneers over there. They were the first group using auricular neurostimulation on infants that had a stroke in utero—hypoxic events. These babies couldn’t feed properly, and they were retraining them to suckle using neurostimulation.

Daniel Powell [00:06:27]:
It’s amazing, because that’s your PhD work.

Navid Khodaparast [00:06:31]:
Yeah, stroke recovery and plasticity.

Daniel Powell [00:06:31]:
And then they end up partnering with us. Their IRB approval for the first clinical study took two years. Ours took two months—because they laid the groundwork.

Navid Khodaparast [00:06:48]:
They paved the road. And we also got our first NIH grant for that—$217,000.

Daniel Powell [00:06:59]:
That was the first grant we ever got.

Navid Khodaparast [00:07:01]:
$217,000.

Daniel Powell [00:07:02]:
I’ll never forget that number.

Navid Khodaparast [00:07:04]:
It was a Phase One.

Daniel Powell [00:07:06]:
So we leveraged that, went to the FDA, and got something called Breakthrough Device Designation—which is a big deal. It’s like fast track status in the pharma world.

Navid Khodaparast [00:07:32]:
It comes with perks—faster reviews, better communication, and long-term benefits like reimbursement potential and coding support.

Daniel Powell [00:07:37]:
So now we're running what we call our FDA study: the SPROUT Trial. How’s that different from our proof-of-concept study?

Navid Khodaparast [00:07:47]:
Well, the proof-of-concept was open label. All the patients got the same treatment. No control group, no placebo. In our world, it’s called sham treatment.

Navid Khodaparast [00:08:13]:
The SPROUT Trial is a randomized controlled, multi-site study. Babies either get active treatment—stimulation to the ear—or sham treatment. Sham means the device looks like it's on but delivers no stimulation.

Daniel Powell [00:08:43]:
Even the person programming it doesn’t know which is which. And babies don’t experience placebo effects. So it’s the best control setup you can have.

Navid Khodaparast [00:08:53]:
That’s where Alejandro was so crucial.

Alejandro Covalin [00:08:55]:
Because even though babies don’t have a placebo response, the person administering treatment could bias results if they knew who was receiving what.

Navid Khodaparast [00:09:06]:
Exactly. Even subtle changes in attention or care can affect outcomes. So both devices have to look identical—same flashing lights, same weight. One just happens to deliver stimulation, and the other doesn’t.

Alejandro Covalin [00:09:59]:
The nurse can’t be able to tell which is which. Everything must be the same.

Navid Khodaparast [00:10:11]:
It’s like the pharma world—active pill and placebo pill must be indistinguishable in look, taste, weight.

Alejandro Covalin [00:10:26]:
But here, the device itself is supposed to give you confirmation it's working. So we had to engineer around that.

Daniel Powell [00:10:38]:
So, what are the primary outcomes we’re looking for in this trial?

Navid Khodaparast [00:10:42]:
With NOWS babies, the goal is to reduce how long they need oral morphine. The standard of care is to administer morphine every three hours, escalating until symptoms are under control, then slowly weaning off. That whole process takes an average of 23 days.

Daniel Powell [00:12:54]:
It’s a long process.

Daniel Powell [00:12:57]:
That’s eight times a day, every day, in the NICU.

Alejandro Covalin [00:13:01]:
These babies stay in the NICU all 23 days.

Navid Khodaparast [00:13:05]:
It’s incredibly expensive—but it’s the only reliable treatment we currently have.

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