Medsider: Learn from Medtech and Healthtech Founders and CEOs - Shaping the Future of Alzheimer’s Care: Interview with Sinaptica CEO Ken Mariash

Episode Date: January 3, 2024

In this episode of Medsider Radio, we had an enlightening conversation with Ken Mariash, a leading figure in the neuromodulation space and the CEO of Sinaptica Therapeutics, where his team is developing groundbreaking treatments for Alzheimer's disease. Their device delivers non-invasive neuromodulation therapy to key networks of the brain and has shown unprecedented improvement in treating this debilitating disease. Ken's two decades of experience leading sophisticated organizations has taken him from management consulting at Charles River Associates to significant roles at CSL, Baxter, and Boston Scientific. During his time at Boston, Ken was instrumental in commercialization and strategy development in the company’s $1B neuromodulation division. In this interview, Ken shares his time-tested wisdom, covering a range of topics from kick-starting a venture and how to approach M&A transactions, to mastering commercialization and best practices for engaging with investors.Before we dive into the discussion, I wanted to mention a few things:First, if you’re into learning from medical device and health technology founders and CEOs, and want to know when new interviews are live, head over to Medsider.com and sign up for our free newsletter.Second, if you want to peek behind the curtain of the world's most successful startups, you should consider a Medsider premium membership. You’ll learn the strategies and tactics that founders and CEOs use to build and grow companies like Silk Road Medical, AliveCor, Shockwave Medical, and hundreds more!We recently introduced some fantastic additions exclusively for Medsider premium members, including playbooks, which are curated collections of our top Medsider interviews on key topics like capital fundraising and risk mitigation, and a curated investor database to help you discover your next medical device or health technology investor!In addition to the entire back catalog of Medsider interviews over the past decade, premium members also get a copy of every volume of Medsider Mentors at no additional cost, including the recently launched Medsider Mentors Volume IV. If you’re interested, go to medsider.com/subscribe to learn more.Lastly, if you'd rather read than listen, here's a link to the full interview with Ken Mariash.

I'm maniacally focused on what's going to move the ball forward in the most productive ways. I'm trying to get 10x return on every dollar that's put into the company. I'm always thinking about there's 20 things we could do. What are the three things that are really going to advance the case for this company? Welcome to Medsider, where you can learn from the brightest founders and CEOs in medical devices and health technology. Join tens of thousands of ambitious doers as a world. we unpack the insights, tactics, and secrets behind the most successful life science startups in the world. Now, here's your host, Scott Nelson. Hey, everyone, it's Scott. In this

episode of Medsider, I sat down with Ken Mariah, CEO of Synaptica. With over two decades of experience in leading sophisticated organizations, Ken brings a wealth of knowledge and expertise to the table. His journey has taken him from management consulting at Charles River Associates to significant roles at CSL, Baxter, and Boston Scientific. During his time at Boston-Kinnua's instrumental in commercialization and strategy development at the company's $1 billion neuromodulation division. Today he's serving as the CEO of Synaptica, a startup making significant strides in Alzheimer's treatment.

Here are a few of the key things that we discussed in this conversation. First, incremental, manageable steps towards your goals is a safer and saner approach. Consider which variables will add more value to your company's current position and be maniacally focused on achieving those efficiently. Second, an early stage company will inevitably have some gaps, and it's not easy to make a compelling M&A case when you have a lot of white space. If you're aiming for an exit, be targeted, appointed champion who will actively align your company's unique value propositions against your target buyer's needs.

Third, for successful commercialization, you need reimbursement, a flawless value proposition, a pitch that clearly shows the superiority of your data and thorough market research. And last, when raising funds be simple and simple. enough so that your investors understand and can articulate your plan well after you leave the room. Okay, so before we jump into this episode, if you're listening to this show, I'm going to make the assumption that you're a dedicated pro looking to learn from the best in the business. If that's the case, which I think it probably is, I've got some exciting news related to our premium memberships. First, let's talk a little bit about MedSider Playbooks, your ticket to going

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Again, that's medsiderradio.com forward slash premium. Okay, here's the second thing. I completely understand that fundraising can be one of the most daunting tasks for any startup, especially in today's environment. That's why we've created a meticulously curated database of investors right at your fingertips. Explore a wealth of VC funds, private equity firms, angel groups, and more, all eager to invest in medical device and health technology startups. Access to this database is a premium member exclusive, so don't miss out.

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All right, Ken, welcome to Medsider Radio. Thanks, Scott. Thanks for having me. Yeah, really looking forward to the discussion, learning a little bit more about your your professional journey in med tech as well as kind of what you're what you're building at synaptica but with that said i recorded a brief bio at the outset of this episode i always like to start here though if you can kind of give us a should have an elevator pitch for you know your background leading up to current role as a CEO of the company that'd be great yeah well scott i'm not going to bore you too much with with my background and drone on and on about my you know my

resume but i did start in consulting and i was taught to you know do a lot of valuation and those consulting days, we worked on some pricing exercises, and it really gave me an aspect of looking at things from an evaluation perspective, which I found really helpful in my later career. I moved into industry. I went to CSL and then Baxter, got a little bit of background in marketing for the first time. And then I moved on to Baxter. I did a lot of portfolio management, strategy, M&A. And then I moved on to Boston Scientific, where I founded the strategy group in the Neuromodulation Division out here in. California and found myself again doing a lot of strategy work, portfolio management, and then looked

at about a hundred different deals on the M&A side, on what I call the buy side. And then finally, one of those deals that we did, I ended up running that franchise as the global commercial head for the Cosman franchise for a number of years. And that brought me to my first startup experience, which was a company called EBT Medical, which makes a non-invasive. with neuromodulation device for a bracta bladder. And then I found my way to synaptica. When I saw the breakthrough announcement, I looked at the data.

I was frankly astounded at the level of efficacy. And having a background in neuromodulation, a little bit of a background in Alzheimer's, and also a background in capital sales, I knew I had to be a part of this thing. So I came aboard officially in March of this year. So tons of experience in the neuromod space, obviously. So that'll be fun to kind of dig into the technology

a little bit more. we're recording this in late, not late, mid-Q-4 of 2003. I think you've been at it with Snaptica for almost a year now. Is that right? Yeah, since March. Okay, since March, got it. So give us a sense kind of for, and if you can frame this up as up, I'm like a, you know, a freshman in high school.

Give us a sense for kind of what the technology does. And then also, you know, if there's any sort of like background origin story that's unique, I guess, please, please hear that as well. Yeah, so it's really interesting how the company got started. it's two Italian scientific co-founders who've been working in non-invasive brain modulation, Alzheimer's, and other neurodegenerative disorders for over a decade. And so our company president, Rich McCarrie, put them together when he saw the amazing science they were doing. They were already collaborating, but he put them together in a company, formed their company. And that became the essence of synaptica, which, as I was saying earlier, you take the Italian sin and aptica, it means without touch, so non-invasive.

So interesting name of the company there. But so synaptica has created a non-drug way of treating Alzheimer's, totally new, unprecedented way of approaching the disease of Alzheimer's using precision network neuromodulation of the default mode network, which is a large brain network that's associated with episodic memory and introspection. Published phase two trial results show we have almost three times the disease slowing power of the newest amyloid drugs with virtually no side effects. and we're about to launch a pivotal phase three trial using this non-invasive treatment for Alzheimer's. There's three things that really make our treatment really stand out as unique. The first is, whereas a lot of neuromodulation is focused on modulating one nerve or one little area of the brain, you think about Parkinson's, you think about the sub-sylamic nucleus, you're stimulating a tiny little region.

We actually think of our therapy as stimulating an entire network. So the default mode network is this large distributed brain network that's associated. with episodic memory and introspection, it's where you integrate your memories. So we're stimulating the entire network. It would be like instead of just a wire in the house, we're lighting up the entire house when we stimulate it. And so that's the first piece. The second piece is we're personalizing. We're using sophisticated algorithms that take into account the patient's MRI and TMS EEG data, which I can go into later, that personalizes therapy. So where we stimulate and how we stimulate has to be calibrated.

in a closed loop manner to make sure we're hitting the right spot on the brain and lighting up the network in the right way optimally to get the right resonance of the network. And then lastly, what makes our therapy different is we're using neuro navigation for precision. So being able to reproducibly come back to the exact same spot on the brain over and over again, week after week, month after month. Ours is a chronic therapy. So precision and reproducibility, especially control. controlling for operator differences is absolutely critical.

So neuro navigation allows us to do that. And so when we combine those three elements, that's what it gives us these stunning results. Unprecedented positive phase two data in mild to moderate Alzheimer's patients. Yeah, super interesting technology for sure. And I'm looking at the website right now, which is synaptica tx.com, S-I-N-A-P-T-I-C-T-X.com. We'll link to it in the full write-up on MedSider up at Synaptica. TX.com, if you want to learn a little bit more about the technology, as well as the, the,

kind of the existing clinical data, as well as the upcoming trials, definitely encourage you to check out the site. But can one follow-up question with respect to the product itself or the system itself. So from a patient experience standpoint, this is an implantable neuromodulation device. I presume like there's, you know, leads that are implanted or like give me a sense kind of for what this looks like from a patient standpoint. Yeah, sorry. So just to back up a little bit. We're using a new form of TMS. So trans-magnetic, trans-cranial magnetic therapy. So we are using non-invasive magnetic fields to induce electrical currents in the brain. So we use a high-powered coil to the back of the head to induce current in the brain. We do that non-invasively

at a depth of a few centimeters. It's actually really interesting technology. But what we're doing is we're adding personalization and precision to this technology that's been around for a long time. The technology is safe and established in depression. So researchers and companies have been using TMS for depression and other neuropsychiatric indications for a long time. There's established coding, coverage, and payment and patient experience is, you know, very seamless. It's totally painless. There's no side effects really other than maybe a headache that resolves. But we're taking that same basic technology. And again, we're adding personalization and precision. Those are the things that really make it different. We're using TMS with EEG. So if you think

about stimulating the brain, when you add one pulse to the brain, it's like dropping a pebble into the pond. The signals reverberate around the brain, bouncing off the walls in a very complex pattern. We use 64 channel EEG to listen to those signals bouncing around the brain, the brain, and that establishes when we've hit, that lets us know when we have hit the right network and that it's resonating in the right way that confirms that we're getting the right target engagement. So it's a novel use of an existing technology combining with TMS EEG and also adding neuro navigation to the picture, again, for personalization and precision. And so the patient experience involves first getting an MRI because we need to know where your brain is in the 3D

space where we're about to stimulate, right? We load the MRI into the neuro navigation system so we can navigate and see where we're going. The system automatically outlines the precunious area of the brain, which is a rather large piece of the brain in the posterior aspects of the skull, which is associated, again, with this default mode network. It forms a central hub. It's like The central hub radiating out to multiple nodes on the network. The precunius is that key hub in the middle. And so that's the target we're stimulating. So the neuro navigation system will show you on the screen where the precunius is roughly,

but where on the precunius do we stimulate? It's a rather large structure. So pinpointing the exact piece of the precunius that gets the right resonance of the network, that is absolutely critical. That's why we use TMS with the EG to confirm we're getting the right. resonance of the network when we stimulate there. Got it. Okay, that's super helpful.

And you mentioned this earlier, synaptica, right, without touch, right? So again, that plays into kind of... Yeah, the non-invasive kind of nature of this technology obviously makes a lot more sense after you described it in more detail. So let's presume, you know, we fast forward, you know, years into the future. This is, you know, this is approved by, you know, regulatory bodies. It's reasonably available. Is this something where I, as a patient, I, as a patient, I can.

go in like once a week, multiple times per week over a course of time? Is that kind of the end goal here? Yeah. So similarly to other modalities that have used TMS in the past, it is an in-clinic therapy, and it involves an induction phase. So the idea is we want to kickstart the brain and we want to get that done in the first two weeks of therapy. So the patient comes back. Once we do the calibration session where we determine exactly where to stimulate and how to stimulate to get the right resonance of the network. Then for 25-minute sessions, once a day for two weeks, the patient comes in every day for 25 minutes each day to get 10 sessions of therapy.

So Monday through Friday, every day they come in, 25 minutes a day for two weeks. Then we back off to weekly. And that was a key insight of our phase two study was we asked the question. We knew we were getting great results with daily studies. stimulation. But that, you know, that involved a pretty rigorous regimen. So the idea was, or the question was, can we back off to weekly stimulation and still get the maintenance of these great effects? In fact, we did. I mean, we achieved unprecedented data that shows that we can slow the disease of Alzheimer's by over 80% on all four primary and secondary

cognitive and functional endpoints. And so the patient would just come back for weekly therapy for 25 minutes, it's totally painless. They're able to recline in a comfortable chair. They can keep their eyes open. They can talk to the technician. They can have a caregiver in the room. They sit back for painless 25-minute sessions. All they hear is like a tapping sound in the back of the head. That's all that they hear. They don't feel anything because we don't have mechano receptors in the brain, as you know, so they feel nothing. Other than maybe hearing the tap, there's nothing else that tells them they're getting the therapy. And the only side effect that we've seen that occurs in maybe 16% of patients is a mild headache that can resolve without any other

intervention within a few hours. That's the patient's experience. And that, again, as I said, has resulted in over 80% disease slowing, which is about three times better than the latest anti-amilid drugs. Yeah, really, really promising. And so again, we're recording this in kind of mid-Q4 of 23. And is there kind of a timeline in mind from when you expect to commence your phase three pivotal work? Yeah. So having published the phase two data and achieved breakthrough status last year, we've really set about raising the funds to get the company, you know, put together and get off the ground. We have spent a lot of time designing our phase three study. We've got an amazing strategic and scientific advisory board that's helped us in the design of the study.

We want to make sure that we can reproduce these fabulous results in a multi-center U.S. and international study. And so we spend a lot of time making sure we get the design of the study right. Secondly, we are working with a hardware partner to use a version of their system that's customized to do our therapy. And so working with that hardware partner to design and to build that therapy has been also a secondary, a big focus for us secondarily. And so we're hoping to launch our pivotal study next year, maybe in Q4 of next year. As you can imagine, as is the case with all of these breakthrough therapies, you know, you pretty much only get one shot to make this right. We've got to make sure that we get this right, given how many failures there have been

in the disease of Alzheimer's, I don't need to tell you, it's been a really tough area to develop in. We're getting some of the best names and advisors on board. we also have a VP of Clinical who's just run a pivotal study in Alzheimer's using neuromodulation. So you couldn't ask for someone who's better placed to run a pivotal in Alzheimer's than Lisa Fosdick, who's part of our team. We're so lucky to have her. And it's not like we, like our scientific founders have not done this before. Giacomo Co. is our scientific co-founder at the Santillochia Foundation in Rome.

he's actually run many studies in Alzheimer's and other neurodegenerative diseases. And he's actually in the middle of another phase three using a drug. So he's no stranger to running phase threes. And our other scientific co-founder, Emiliano Santarnacki, who is at Harvard MGH, he's also run many studies in non-invasive brain modulation in various disease states. So, you know, we've got a pretty accomplished team here. We've got great advisors. And we're looking to get that off the ground.

next year. Got it. Yeah, very, very impressive tackling a really significant problem with not a lot of available available solution. So with that said, let's use the next, you know, 20, 30 minutes or so to kind of go in time. And really, I'd love to kind of, you know, pick, pick your, pick your brain a little bit, right, since we're on the topic of cognitive function and learn a little bit more about kind of your experiences over the years and in your various roles. So let's start first with, with like kind of the early phases of a startup, right? Maybe even a little bit earlier than where you're at with Synaptica, it's oftentimes quite challenging for most entrepreneurs, founders, CEOs,

where you're trying to get to that next milestone, right? That next phase of development with pretty limited capital for the most part. You know, most startups, I think you agree, you've been around. A lot of them aren't flushed with capital in those early days. So kind of with that in mind, where do you think most founders go wrong? Or most CEOs go wrong in those early stages? or, you know, if you want to flip that, that question around, you know, where, where any, what are like one to two pieces of advice that you often, you know, find yourself recommending or advising, you know, other startups and how they can kind of move quickly, yet still be efficient with capital in those, those early days. Yeah. So I appreciate the question. And unless you are Elon Musk and you're raising 280 million for Neurlink, let's just assume that as the usual kind of startup executive and team, you're kind of,

limited capital. And so I'm focused maniacally on creating incremental value in a sequential fashion. A lot of a lot of entrepreneurs that I've seen. And remember, I've been on the buy side and the build side are kind of focused on doing it all at once. And either they make the mistake of thinking that they can do too much with limited people resources and financial resources, or they try to raise a huge round and try to do everything, you know, with a monster series A. And that's usually not what happens. And so I'm maniacally focused on what's going to move the ball forward in the most productive ways. I'm trying to get 10x return on every dollar that's put into the company, right?

And so I'm always thinking about there's 20 things we could do. What are the three things that are really going to advance the case for this company? It might be a proof of concept study in animals. It might be a piece of IP that we need. It might be a hardware partner. I'm trying to think it might be a team member that's kind of a key piece that we're missing. So what are those little incremental things we can do to add value to the company? Because it is a sequential, slow, deliberate process for most startups.

And so, again, just, you know, instead of thinking that, you know, money is going to solve all our problems, If you just give me $50 million, I can deliver all of this. It's better to think through, I think, what are some milestones that are get us there with a $10 million chunk, a $20 million chunk, another $20 million chunk? What are those steps incrementally? So that's kind of how I would help some startups think through, you know, planning their incremental, sequential approach to value creation. Yeah, I love that. I love that framework. And even that example that you shared of like, you know, you've got your top 10, maybe top 15.

kind of potential milestones that you could hit, right? But some of those are going to be further out. Some of those are going to require a lot more capital. But thinking through kind of what are your top three and how can I get there, you know, with the resources that I currently have versus, you know, what resources I'll need in the future to, you know, to tackle those next top three as an example. And here's a perfect example. We can spend a lot of time thinking through commercialization.

And we do spend some time thinking through commercialization right now. But rather than spend a ton of money, validating, you know, I could spend hundreds of thousands of dollars on market research and branding and hiring a VP of sales. It's just not the right time for us to be doing that. We need to be thinking through at a basic level or go-to-market and we do have a plan there. But really focusing on the key things in front of us that are going to advance the company, that's got to be the Monarchal focus, you know, Monday through Friday, Saturday and Sunday, maybe we can start thinking about those other things. But, you know, for the 60 hours that we're

focused on, you know, those key value creation of activities, maybe we spend another 10 or 20 hours beyond that thinking through the next steps beyond. Right. Yeah. And I, if you're, if you're tracking with this conversation so far, we recently released an episode with Bill Colon, who's another serial entrepreneur on the West Coast here. And, you know, with a lot of the, they have kind of a unique kind of framework around a lot of the projects that he focuses on. But like, he always starts out with, you know, my seed round needs to get to this certain milestone, right? And that, that's sort of what he's working on doesn't fit within the parameters. He's likely not even going to work on the project. And so that's just a really, really helpful framework. And it reminds me,

even like personally, right, we're in the process of preparing for a series B fundraise with Fastwave. And that's probably then, you know, the top two or three questions that often come up from investors is like, okay, you're raising X amount of money for this, you know, this particular capital raise. Like, what are you going to do with it and show me how you're going to get there, right? And if it's If your answers to that question are out of whack or they don't, they're not easy to follow, you need to kind of go back to the drawing board, right? Which is in line with kind of your, you know, your quote unquote maniacal approach to kind of in a serial fashion generating value, right, incrementally along a certain, along a certain

pathways. So I really, really love that framework. Let's jump to kind of the next topic, which is, you know, you're right in the throes of a lot of clinical and regulatory work. You've got really novel technology at SNAPTC. that that's I mean the Ray Klan kind of process in general can be kind of daunting I think for a lot of a lot of founders and CEOs but especially so with you know very novel kind of innovative innovative systems like you're working on so when you think about kind of how to how to effectively map that out right and and build out

kind of this this function right in order to get to the next you know Klin reg milestone what how do you typically approach that or what are the kind of the top top pieces of advice that uh that uh that you typically recommend other people kind of in the same boat. Hey there, it's Scott, and thanks for listening in so far. The rest of this conversation is only available via our private podcast for MedSider Premium members. If you're not a premium member yet, you should definitely consider signing up. You'll get full access to the entire library of interviews dating back to 2010.

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