Shaping the Future of Alzheimer’s Care

Researchers have been looking for a cure for Alzheimer's disease for decades, with little success. Traditionally, the arsenal we’ve been using is largely reliant upon drugs. But could a device, not a pharmaceutical, be the key to Alzheimer's treatment? This is a possibility that Ken Mariash and his team are solving for at Sinaptica.

Ken is a veteran in the medical device space. He started his career in consulting, where he honed his skills in valuation and pricing. He then transitioned within the industry to roles at CSL and Baxter, delving into marketing and gaining exposure to portfolio management, strategy, and mergers and acquisitions (M&A). His tenure at Boston Scientific was an important chapter in his career, where Ken not only founded the strategy group in the neuromodulation division but also led the global commercial group of a major franchise. This breadth of experience that includes being on both sides of a business — the buy-side and the build-side — positions Ken as an asset in navigating the complexities of business strategy and development, which is what he’s doing as the CEO of Sinaptica.

Sinaptica, under his leadership, is developing a non-invasive, personalized neuromodulation treatment for Alzheimer’s disease. By stimulating the Default Mode Network (DMN), Sinaptica aims to restore balance and function to the Alzheimer's-affected brain. It's a promising shift from the usual amyloid-based drugs and a new direction in tackling Alzheimer's along with potentially other neurological conditions.

Sinaptica is the brainchild of two Italian scientists specializing in non-invasive brain modulation and neurodegenerative disorders. Recognizing the potential in their groundbreaking work, Rich Macary, who now serves as the company’s president, brought them together under the banner of Sinaptica. A tribute to their origin, and the company’s non-invasive methodology, Sinaptica’s name is coined from the Italian words 'sin' and 'aptica,' translating to 'without touch'.

Sinaptica uses repetitive transcranial magnetic stimulation (rTMS) therapy by specifically employing non-invasive magnetic fields to induce electrical currents in the brain. This is not a completely novel approach to the disease, but there are three main aspects that set Sinaptica apart from the rest. 

First of all, Sinaptica primarily focuses on neuromodulation of the Default Mode Network (DMN), a brain network that is responsible for episodic memory and introspection. Secondly, their neuronavigation is enhanced with TMS-EEG for better precision of the therapy. And thirdly, they personalize the treatment through advanced algorithms based on the MRI data of each patient.

Thanks to these improvements, Sinaptica was able to demonstrate extraordinary phase 2 data in patients with mild to moderate Alzheimer's, showing an unprecedented 82% – 84% slowing of cognitive decline, exceeding the 27% – 29% achieved by the latest amyloid-based drugs. The results of the study were published in Oxford’s prestigious Journal, Brain. In a nutshell, this non-invasive treatment, which requires an initial induction phase followed by weekly sessions, offers a comfortable experience to patients as well as promising results.

Thanks to their groundbreaking findings, Sinaptica has earned the prestigious FDA Breakthrough Device Designation, which recognizes the therapy’s potential to revolutionize Alzheimer's treatment.

Sinaptica is currently gearing up for a pivotal phase 3 clinical trial, aiming to replicate their remarkable results on a larger scale. This crucial study, scheduled to launch in the back half of 2024, will define the potential of Sinaptica's therapy to become a game-changer in the fight against Alzheimer's.

Key Learnings From Ken’s Experience

• Incremental, manageable steps toward 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.   
• 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. Identify a champion who will actively align your company’s unique value propositions against your target buyer’s needs.
• For successful commercialization, you need reimbursement, a flawless value proposition, a pitch that clearly shows the superiority of your data, and thorough market research.
• When raising funds, be simple enough so that your investors understand and can articulate your plan after you leave the room.

Incremental Value Creation

Ken will tell you that unless you’re Elon Musk, you likely have limited capital to work with when you first start a company. While some entrepreneurs like doing it all at once, Ken is all for creating incremental value in a sequential fashion.

In Ken’s view, overreaching with limited people and resources or attempting to secure a massive round of Series A funding and trying to do too much with it is overly ambitious. Instead, he recommends being “maniacally focused on what's going to move the ball forward in the most productive way.”

While successful capital raising is undeniably useful, money doesn’t solve everything. Ken says, “I try to get a 10x return on every dollar I spend.” The real challenge lies in identifying incremental steps that enable significant achievements with relatively modest investments, whether it's a proof-of-concept study, securing intellectual property rights, partnering up with hardware manufacturers, or recruiting key team members. Focusing on small, well-thought-out steps often leads to success without overwhelming the mission. 

Clinical studies are the perfect field to apply this mindset. Medtech startups often grapple with designing clinical studies that maximize returns on multiple fronts. Ken likens this to solving a multivariate algebra equation, balancing regulatory requirements, reimbursement strategies, physician marketing, health economics, patient needs, along with other factors. 

“It's all about balancing what's achievable versus what would be nice to have,” Ken says. Ticking off multiple boxes with one study is lucrative, but it's unrealistic to expect to cover all bases in a single stride. Moreover, trying to do so — unless you have real leverage that works across multiple fields — almost certainly makes the study very complex and too expensive. 

Ken's strategy redefines success not as a grand, singular achievement but as stepping stones leading to smaller victories. He prioritizes achievable, realistic goals over grand ambitions, focusing on generating substantial value with each step. This proven strategy is as realistic as it is pragmatic.

Conversations with Strategics 

“I looked at hundreds and hundreds of deals at Boston Scientific, and I was privileged to see some of those go through and see a lot of them not go through,” says Ken, who has experienced firsthand what makes a transaction succeed and what causes it to falter. 

In the early stages, it’s natural to have some gaps in your operation. However, “Selling a concept that has a lot of white space is challenging,” shares Ken. To navigate this, it's crucial to align with your target acquirer's needs, leveraging your strengths accordingly. 

For that, Ken recommends finding an internal champion who can effectively leverage your unique value proposition, whether it's commercial call points, specialized expertise in a therapeutic area, or technical product knowledge. The key is to focus on something that complements the existing strategy of your target company and aligns well with your existing strengths.

Surprisingly, the best champion for this often doesn’t come from the business development (BD) department. The BD team may assess and negotiate the deal, but you need someone whose job will be actively selling it from the strategic’s division. This could be a marketing professional or even a product manager, someone who believes in your product's fit with their existing portfolio and is convinced they can commercialize it. Ken reiterates, “Obviously, you have to have a great story and a great pitch, but having an internal champion is what a lot of people miss.”

Ken also offers practical advice on the timing of M&A deals. Convincing a healthcare giant to invest R&D dollars into your project is quite a challenge. These companies generally aim to steer clear of ventures that might dilute their profit and loss (P&L) statements. If your company is too early in its development and requires heavy R&D investment, making a compelling case for it can be difficult. Ken suggests that the most strategic time to approach is when you're on the brink of pivotal data, thereby minimizing the burden of R&D.

And lastly, Ken recommends engaging with multiple potential buyers at once to create a competitive environment or a "bake-off".

While Ken's insights are invaluable for navigating the complexities of M&A transactions, finding a champion for your venture, and striking at the right time, it's also important to remain flexible and open to other avenues. As Ken points out, certain scenarios require a reassessment of your end goal. In some situations, companies grow too quickly and become too expensive for acquisition. So, if a company is growing exceptionally fast and has the potential for an IPO (Initial Public Offering), an exit via M&A might not be the best decision.

The Four Pillars of Effective Commercialization

When it comes to commercializing a product, Ken breaks it down into four actionable steps.

Firstly, reimbursement is crucial. Understand who will pay for your product and map out the route to secure coding, coverage, and payment. “Being able to do finger-painting exercises for investors to show the pathway to coding coverage and payment is absolutely critical,” says Ken.

Secondly, you need a flawless value proposition. You should be able to explain why someone should buy your product in one compelling sentence. “If you can't answer that question in one line succinctly and powerfully, it's not a good value proposition,“ Ken warns. 

The third piece of advice is about how you position data. Medical devices are developed in relation to data — whether it's from clinical studies, patient information from an implantable device or a wearable, or other patient reports. Ken says, “The data is always the enamoring thing about these new products, and yet if the insights aren't actionable, it's actually more of a distraction.” Therefore, it's essential to not only collect data but also clearly define how the data supports your go-forward plans.

Fourthly, and perhaps less obviously, relates to the role of market research. While traditional market research has its place, Ken suggests a more direct approach: talking to sales reps. Engage with salespeople who have sold to your customer and patient segment and learn how they would position your product, how they would market it to physicians and staff, and ultimately, how it would be presented to patients. This real-world feedback is often more valuable than extensive market research. “Instead of spending hundreds of thousands of dollars on a research project, you can just talk to five really good sales reps and probably get more value out of that deliverable,“ Ken adds.

Simplifying Fundraising

When it comes to fundraising, Ken emphasizes the need for a plan that's not only great but is also simple enough to be easily understood and remembered, even over a casual dinner conversation. "Investors should be able to articulate your plan effortlessly to their partners at home. It's all about making it simple and digestible," he explains.

Ken also underlines the importance of answering the question: why now? In the world of investment, there's often a tendency to wait and see. To counter this, you must create a sense of urgency and movement. Ken recalls a lesson from a mentor, "We chase what moves." It's about convincing investors that the ground is shifting beneath their feet, that a megatrend is passing by and they have to decide right now whether to join or miss out. "That's crucial for gaining traction with your fundraising efforts," he advises.

While it's important to delve deep into data, especially in healthcare, Ken emphasizes the necessity of bringing investors back to the core, intuitive idea. After analyzing the data, remind your investors of the simple, key concept of why you're doing this. This is about hot cognition, where a straightforward idea resonates and draws people in, as opposed to cold cognition, which is getting lost in the data. “Coming back to that, it will stick in their mind, like a key that opens a lock,” says Ken.

In essence, if you can strike the right balance between detailed data and a compelling, simple narrative that sticks in the mind — while creating a sense of urgency and movement that compels action — you’ll set yourself up for a lot of interested investors.