Rewiring Recovery: Advancing Nervous System Repair With NervGen’s Mike Kelly
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Hello, this is Richard Jacobs with the Finding Genius Podcast, now part of the Finding Genius Foundation. Our guest today is Mike Kelly. He's the CEO of NerveGen. So we're going to talk about nervous system repair, spinal cord injury repair. It should be a very interesting call. So welcome, Mike. Thanks for coming. Thanks, Rich. Thanks for having me. Yeah, yeah. Tell me a bit about your background before we get into the work you do at NerveGen. Sure. So I've been in...

pharmaceuticals for roughly 30 years. I started out at a large company, TAP Pharmaceuticals, 30 years ago on the commercial side of the business. Was there for many years and then ultimately jumped out into the world of startup pharma companies with companies like ViroPharma and Guilford Pharmaceuticals and then on to pure startups, which are companies like Azure and Adapt and Covus. And as I

progressed throughout my career, you know, gaining knowledge of all the different commercial aspects of the business. I started to get into general management and had, you know, my last job was with a company called Adapt Pharma, a privately held company where we developed and launched Narcan nasal spray in the U.S. and Canada. That was the opioid reversal agent, which, you

has a lot of similarities to NerveGen as far as significant unmet medical need that we're trying to attack and a small team who's working hard. Okay. So yeah, NerveGen right now, what conditions are you looking into? Is it like spinal cords being severed or damaged or what conditions necessitate your work and your products? Yeah, sure. Our technology is fantastic.

comes from the work from Dr. Jerry Silver, who recently died this year, actually. He was a pioneer in nervous system regeneration, nervous system disorders. And Jerry's work was really centered around a group of molecules that he discovered were inhibiting repair in the central nervous system. And through that discovery, he started to look at how could you turn off this inhibitor

and allow nerves to regenerate. And the technology that led to the discovery of MBG291, which is our lead product candidate that's currently in clinical development. And the animal version of MBG291 has been studied in multiple different disease models, ranging from chronic spinal cord injury, acute spinal cord injury, peripheral nerve injury, optic nerve,

multiple sclerosis with a demyelination study, as well as stroke. So there's multiple areas that we could have gone into. When I first joined, we were actually looking at all of these different areas, but we focused our efforts now in the clinic with human studies and spinal cords.

So we're currently in the middle of conducting a study with people who've suffered from a spinal cord injury and have paralysis. Okay. So have you developed a protocol to help them or what's the story?

Yeah, right now it's a phase 1b2a clinical trial. There's two arms to it. There's the first group of patients are about 1 to 10 years post-injury. The second group of patients are between 20 to 90 days post-injury. The reason we stratified those different patient populations is because the preclinical animal models have demonstrated effects in both of those types of injuries, a chronic injury and a subacute injury, which is what we're calling it.

So the protocol looks at both of those patients. They're enrolled into the trial. They're randomized to go on either a drug or placebo. The study's 16 weeks long. The treatment period is 12 weeks. And we're measuring things like connectivity. Does the connection between the motor cortex of the brain and the hand and the legs by sensory measurements on the muscles, does that signal actually improve? We're also measuring functional improvements, which are

10-meter walk test, nine-hole peg test, upper and lower extremity motor function scores to see does that signal translate into functional improvement. So we completed enrollment in the chronic cohort, the people who have injured between one and 10 years ago, and

That study, the last patient will be finishing the study in the next month, and we'll have a data readout on that patient population in early June. And then the second group of patients is currently enrolling, the SevaQ population. And so we'll know likely sometime next year whether we work in that patient population and if there's a difference or if we work better in one population or the other. Okay. So again, what is the protocol for healing? What does it look like?

Well, the protocol I just mentioned, the protocol is basically we're measuring specific muscle groups as far as signals, the electric signal going from the motor cortex of the brain to hand sensors on the hand and leg. So the primary endpoint of the protocol is to see does that signal get stronger? The secondary endpoints, as I mentioned, there are six functional endpoints ranging from walking speed and upper and lower extremity motor functions.

So we don't know right now because the study is enrolling and it's a blinded study. We won't know until we unblind the data in June to see if we do have that effect. Okay. Again, what do you expect the effect to be? It's just...

I mean, what was it like clinically? Yeah, we're hoping clinically, you know, that we see things that we saw in the animal models, which is improved motility, improved function, improved signaling and improved, you know, giving folks the ability to move and have coordination if we can remake those electronic connections by hand.

enabling the nervous system to repair itself. So that's the goal. Okay. Again, what would a repair look like? Like what the myelin sheath around the nerves is destroyed? I mean, what are the details here? What happens in these situations? Again, what does a repair look like? So when somebody damages their central nervous system or their spine, axons get crushed. And molecules called CSPGs inhibit those axons from reconnecting. The

the myelin around the axons also gets damaged. So the signal can't get through. So if your brain says, I want to move this pencil with my hand,

you can't do that because the signal's not going from your brain to your hand. So the goal here is to see, can we actually remyelinate, regenerate, enhance plasticity of the central nervous system to allow the signal to get through? And then we'll be measuring that specific signal through what's called electrophysiology. You can specifically measure it with what's called an MEP amplitude, a motor evoked potential amplitude measurement.

and the strength of that amplitude. We can also then see, can somebody do a nine hole peg test? Meaning, can they take pegs out of a board and put them into a tray and then take them out of a tray and put them back into a board? And does that progress over time? Can they speed up that progress of coordination

and functional movement of their hand. So that's an example of one of the endpoints, two of the endpoints, the electrophysiology endpoint and a nine-hole PEG test, which is one of the secondary endpoints. So what it looks like is, you know, the person who is paralyzed, who doesn't have function of their hand,

If we can measure the improvement of the signal to their hand and then measure the actual functional coordination of their hand, those are the types of things that we're studying. Okay. Again, is there going to be trials in rats or heavy dried organoids? Or how does anyone know there's going to be any efficacy to this? There's a ton of...

data that in the preclinical models, as I mentioned, ranging from acute spinal cord injury to chronic spinal cord injury, stroke, multiple sclerosis, peripheral nerve injury, these are all animal models, right? So Dr. Silver and Dr. Lang did publish a study in Nature. Dr. Rink

published a study in experimental neurology. There is a bibliography up on our webpage that folks can go to and look at all of the different preclinical models and preclinical studies. We have some fantastic videos up on our website to show that when you paralyze a rodent,

and you treat them with placebo versus treating them with the drug, that they do regain coordination and function, and they can actually walk and run in climb ladders as opposed to the placebo-treated animals who have no functional movement of their hind limbs. So the goal here is to see, can we translate a fraction of what we see in animals into humans? And if we can, it'll be a breakthrough in science. Okay. I mean, do you expect full repair or partial repair or what?

Well, we don't know. We see a pretty significant response in animal models. There's a score called the BDB score in animal models where

The placebo group that was paralyzed got back to a score of around eight, which is occasional coordination, as opposed to the treated group that got back to fine motor movement and approaching normal function. So they didn't get to normal function, but they got up to a score of 15 out of 21. So it's a pretty significant shift in motor movement in animals. And

that's what we're hoping that can translate into humans. Okay. So what are you, you're in clinical trials? Are you in like stage one or where are you at and how long of a runway is there until this happens? So the trial that I just talked about that we're currently enrolling the two groups in, the subacute cohort and the chronic cohort, that is underway. The chronic cohort is fully enrolled and

And we will know data in June, early June. The subacute cohort that's currently enrolling, we will likely know later.

So, yeah, we're only two months away from knowing if this drug translates from animals to humans. I know. That's great. Are you going to be doing any organoid models or are you just going to go through animal models and then the human trials? Well, this is a human trial that we're conducting now. So there's no reason to go back into the preclinical stage. So we're going to be, you know, if this data is positive, we'll be sitting down with the FDA to talk about the next stages of development. Yeah.

Yeah, that's great. But what's the runway from here? How long until you know the results of the trial and you're able to commercialize it, get it into clinics? So the trial readout, like I mentioned, will be in June. So right now it's end of March, March 28th. So we have two months before the trial will read out. From there, we'll sit down with the FDA and we will present the results to them and we

It really depends on the robustness of results here. So if we see that the biomarker that we're using, which is improved signaling, also relates to the functional endpoints that we're looking at, and there is a connection between improved signaling, improved function, that'll be a breakthrough in science. So we'll be asking for a breakthrough. We'll be proposing a very fast time to approval.

And, you know, obviously if the FDA requires us to do a study, then we're going to have to do another study and it'll likely be a phase three. That's going to be another version of what we're currently conducting, but we will focus heavily on the functional endpoint. So this study, the primary is electrophysiology. The secondary is functional that we're doing today. We will reverse that and do a functional endpoint supported by electrophysiology as a secondary endpoint in certain centers.

And it'll be a multi-center, several hundred patients study to be able to, you know, pull together a new, you know, the cornerstone of a new drug application that will submit to the FDA for approval. Is there any chance that it...

overactivates some neurons and underactivates others, like it doesn't apply evenly or it causes, again, overactivation in general? No, this isn't. So the unique mechanism of this drug, we have a lot of biological data. We're actually looking right now

We're doing a lot of work on the molecular mechanism of action, so more to come on that. But the biological effects that we've seen and that they've demonstrated in animal models is that we really only turn off the inhibition of CSPGs where they are inhibited.

So CSPGs are ubiquitous throughout the body and they are the cement that holds your central nervous system and nerve network together in your spine. And it has not demonstrated any effects on normal CSPG activity. It only has demonstrated effects where CSPGs are inhibiting repair. Okay.

So, I mean, yeah. You expect that's great that there's no real bad side effects. Are there any other side effects that appear to be happening so far or no? Sure. We did a phase one study and there were no serious adverse events. We did see injection site reaction. This is a peptide, which is injected deltoidally.

daily into the belly fat subcutaneously, similar to insulin that's a peptide. And we did see some ejection site reaction, but that's really all that we saw. The drug was well tolerated across all doses in our phase one. There were no treatment discontinuation, no serious adverse events, no clinically significant effects that were related to treatment. Yeah. I mean, it seems like the path from here is close and pretty clear.

Once this is cleared, where is it going to appear? I guess as part of a neurologist would be one to prescribe this protocol or how would people clinically access it? Well, we got to get to FDA approval first, right? So if this drug is ultimately FDA approved, I believe that physicians, probably physical rehabilitation physicians who are working with people with spinal cord injury on a daily basis will be looking to prescribe this to their patients.

Right now, our key opinion leaders that are working in this space are heavily focused on rehabilitation. Monica Perez, who's our primary investigator at Shirley Ryan Ability Labs, is...

is an expert in electrophysiology, but her team is also working at Shirley Rhyne, which is the number one rehab hospital in the U.S. and possibly the world for the last 30 years. So it'll be heavily used in rehabilitation medicine. Does it matter where on the spinal cord an injury occurs? Like, you know, if it's near the cervical vertebrae near the top or the bottom lumbar, you know, thoracic, any difference in efficacy that you can say?

We're studying, right now we're studying cervical. We haven't studied anything else. This is our first human study. It has been studied in cervical and thoracic injuries in animals, and there's effects in both. But we're studying currently C4 through C7 specifically in this clinical trial. Well, very good. So how can people keep tabs on the process since it's...

you know, literally, I guess, not an exact science on when it'll be ready, but over the next year or two, perhaps more.

How can people keep tabs on this to see when it becomes clinically available or approved at least? Yeah, and nervegen.com. If you just tap into our website, www.nervegen.com, you can see, follow all of our progress. We put out press releases on all of our key milestones. I believe you can sign up for emails when we do have a press release go out. It'll automatically be generated to your inbox. Okay, well, very good.

Well, thank you very much for coming on the podcast. And it sounds like it's going to be a huge game changer and hopefully it'll get there very soon. So again, thank you for coming. Thank you, Richard. Have a great day. If you like this podcast, please click the link in the description to subscribe and review us on iTunes. You've been listening to the Finding Genius Podcast with Richard Jacobs.

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