Ken Mariash, Sinaptica Therapeutics - Spotlight Studio | LSI Europe '23

Transcription

Nick Talamantes  0:16  
I'm here at LSI Europe in Barcelona with Ken Mariash of Sinaptica Therapeutics, Ken, thank you so much for joining me in the studio. 

Ken Mariash  0:23  
Thanks for having me. 

Nick Talamantes  0:24  
So why don't you tell me a little bit about Sinaptica? 

Ken Mariash  0:27  
Yeah, so Sinaptica is developing a totally new way of treating Alzheimer's. It's a drug free, non invasive neuromodulation approach. It's focused on modulating a new network in the brain that we've identified. So associated with episodic memory. It's the default mode network. And we're lighting up that network with massive amounts of magnetic field that induce current in the brain, but non invasively. And so the patient comes back every week for 25 minutes sessions. And we're strengthening the network. by inducing neuroplasticity in that network, we're basically counteracting the disease process of Alzheimer's by strengthening the neurons in the network, and thereby bending the progression of the disease. And we're showing 82% slowing of the disease and mild to moderate patients in six months. Really incredible result. In my view, it's unprecedented.

Nick Talamantes  1:15  
I've seen that you are a seasoned veteran within the neuromod space. There are a lot of innovators and innovative companies in neuromodulation. Today, why come to snap Tikka? 

Ken Mariash  1:26  
Yeah, so I love neuromodulation. I love the idea that it's targeted therapy, you know, you take a drug and injected into a vein, it goes all over your body with all kinds of unknown side effects, right? With neuromodulation, we can be very precise in what we're hitting, and what the waveform is that we're delivering to the body, and having a modulation effect on big biological systems and organ systems in the body. So I've always loved neuromodulation. But what is cool about where neuromodulation is going, is that it's going non invasive, or at least less invasive, we're no longer necessarily having to put leads in the brain, for example, to target certain structures, we can hit those structures non invasively. And so my last startup was a non invasive. And this startup was also capitalizing on three areas where I feel like I have a lot of experience, one capital sales to neuromodulation, and three, Alzheimer's, I've had two previous experiences and Alzheimer's. And so this will be my third spoiler alert, the last two failed.

Nick Talamantes  2:28  
Third time's a charm, Third time's a charm. How to Sinaptica different differentiate itself, then from some of the other early stage companies that are developing solutions to treat patients with Alzheimer's?

Ken Mariash  2:42  
Well, we've been trying to for a long time, target amyloid. And decades, and billions have been spent targeting amyloid. And it's sort of like cleaning up the ashes after the house has already burned down. I mean, there's something in the disease process that involves amyloid. And we're not sure exactly where it comes into play, but it's probably more of a covariant than a cause. And so now we're starting to look at different mechanisms. You know, I call amyloid like the usual suspects, right? So we're going beyond that. And as I said, the default mode network is this brain network that is responsible for episodic memory, and introspection. Now, think about this, where you integrate your memories is in the default mode network. So you're building this internal, this internal narrative, this sense of self. So it's not an overstatement to say that this might be where our sense of self is built. Alzheimer's patients will often report in the early stages of the disease that they no longer feel like themselves, they say, I no longer feel like myself, There's something strange. I feel like I'm not me anymore. And so, you know, that's sort of a clue that something is disconnecting. And we think it's the default mode network, which is very strongly correlated with a disease progression. And so this is all new. All previous attempts at Alzheimer's stimulation have involved different targets, and none have involved personalization and precision. We're taking a targeted approach to this, where you stimulate and how you stimulate is critical, in our view to getting these spectacular results.

Nick Talamantes  4:10  
Is, is it a treatment that needs to be continuous? Or is it enough to just come in for a session every now and then as as required and get the same benefits?

Ken Mariash  4:21  
Yeah, I mean, a lot of neuromodulation in the past has been focused on daily stimulation. These are elderly patients. The question we were trying to ask in our Phase Two was can we back off to weekly stimulation and still get a good result? So our paradigm involves jumpstarting the brain by doing daily induction and we do that for two weeks daily. And then we back off to weekly stimulation. And you know if it was my mother, which it could be, actually, I would get her in the in the car and I would drive her to her sessions if it meant the difference between her being in a nursing home and forgetting my name, versus holding on to her sense of stuff and living independently? Of course I would. So although it may seem like a bit of a burden to come in every week, it's certainly less than dialysis and dialysis patients are 92% compliant. So the dosing regimen we believe is acceptable for most patients, if all that means is preserving the essence of who you are. Absolutely, people will comply.

Nick Talamantes  5:21  
So I know that you've been to an LSI event before you're here in Europe. Now after joining us in Dana Point earlier this year, what made you decide to come again?

Ken Mariash  5:32  
Besides the invitation? And besides the fact that it's in Barcelona, I think you guys put on one of the best, if not the best shows in medtech, and everything runs like clockwork, you have some of the best investors here. The logistics are incredible. The social media presence is really interesting, too, because you create a lot of virtuous cycle with the social media that you have out there. And the event last night was a lot of fun, too. We were at a castle, basically, you don't really see that and a lot of

Nick Talamantes  6:05  
conferences, or flamenco dank dancing for that matter.

Ken Mariash  6:08  
Yeah, amazing. Now you guys put on the best show in medtech. 

Nick Talamantes  6:12  
So maybe coming back to where your company is at currently and where you're going. Are you currently in human trial? Where at what stage are you guys at right now?

Ken Mariash  6:22  
Yeah, so we published as I said, unprecedented phase two clinical trial results, Sham controlled, double blind, six month results that are published in the prestigious journal Brain, which is out of the Oxford University Press. So we feel really good that that's a solid proof of concept study. It's a landmark study, haven't seen anything like it, not only did we achieve 82% slowing in the primary, we achieved over 80% slowing of the disease on three other secondaries, both cognitive and functional. And then you may be wondering, do we actually change the brain we do. We not only do we change the signaling of the brain by raising gamma levels in the brain, but we also preserve the evoked potentials in the brain. And then this is interesting, we have imaging data now that shows that we create new connections in the brain where we stimulate and across the network, we also preserve the micro cortical structure as measured by this thing called angle R, which I could talk your head off about. And then lastly, we preserve gray matter volume. So the sham arm and the active arm both decline, but the active arm declines less. So we're preserving gray matter in the brain, we are literally changing the brain. So your question was about where are we going next, we're full steam ahead towards pivotal. We believe that we can march forward with this data and replicate it in a multicenter us EU study with a one year endpoint potentially, that will make this state of the art therapy available to patients in the US first and around the globe thereafter.

Nick Talamantes  7:53  
And I imagine that in order to get to Pivotal, you're going to be raising money, as

Ken Mariash  7:57  
as always is the case, you know, you're never you're never not raising. We're really happy to announce we closed our seed round, and it's oversubscribed. We have the participation of some name brands that you'd recognize a few of which we'll be making public soon. And now we're in process on a Series A that will fund that journey, build our clinical device and initiate the pivotal trial next year, which will take us through FDA clearances. 

Nick Talamantes  8:23  
So is there any advice that you would give to your peers in the neuromodulation space who are looking to bring a product that's addressing a severe unmet need like yours?

Ken Mariash  8:32  
There's a lot of advice. Just one piece? Boy, I've had to pick one thing like what's your what's your bumper sticker? What's your billboard gonna say? You know, what I found is who's on the rowboat is absolutely critical. You got to get the right people in the rowboat. Because you're fighting for your life. And everyone's got to be rowing in synchrony. And it does get tough. And you have to like who you're working with. And I love my co founders. And I love the team that we've built. You know, we have a fantastic VP of r&d who's literally built a system like ours before from the ground up. We have a VP of Clinical who's just run a pivotal study with neuromod in Alzheimer's, there's only one person on the planet like her. And she is a fantastic fit for the team. So getting the right people on the bus is critical. And because you're going to spend the rest of well hopefully your journey will be a long one the rest of your journey with these people usually.

Nick Talamantes  9:29  
So then how do you meet the right people that?

Ken Mariash  9:33  
Yeah, I mean, everyone has a network and you know, six degrees of separation in the med tech space is more like two degrees of separation. So we all know, in our networks, a lot of the right people, keeping the word out using the network, letting people know that you're looking and don't be afraid to put it out there and, you know, work your network as much as you can to get a few levels deep to find the right people

Nick Talamantes  10:01  
Ken this sounds like an incredibly promising treatment option for many patients with Alzheimer's disease I thank you for stopping by the studio and telling me about it.

Ken Mariash  10:10  
yeah thanks for having me