Ken Mariash Presents Sinaptica Therapeutics at LSI USA '23

Transcription

Hi, I'm Ken Mariash, as she said CEO of Sinaptica Therapeutics, here to tell you about our revolutionary non invasive neuromodulation therapy for Alzheimer's, which is achieved unprecedented phase two clinical trial results, results which are better than any drug we're aware of. Alzheimer's is a thief that robs us of everything it means to be human. In a recent Milken Institute study, they found that Alzheimer's was the most feared disease ahead of cancer, stroke and heart disease combined. Not only does Alzheimer's robbed the life of the patient, it also totally engulfs the lives of those around them. I know because I have a personal connection to the disease. Researchers have spent decades and billions fighting the usual suspects, amyloid and tau, which started to accumulate early in the disease progression, and yet they plateau even as the disease continues. Well, drugs like Locanda Mab do a great job of clearing amyloid, maybe there's something more to the puzzle. Maybe there's something that we're not seeing, maybe amyloid is more of a covariant or a contributor than the real cause. Our scientific co founders have focused a decade on answering that very question. Giacomo is the director of the Central litsea brain stimulation laboratory in Rome, and his colleague Emiliano is the director of the precision neuroscience and neuromodulation program at Harvard mgh. They've been looking at Alzheimer's in a very different way. Giacomo and Emiliano and others have been looking at Alzheimer's more at the synaptic and network function level more as an electrical disorder. Now, just as we think about cardiac disease is having electrophysiological components just as much as mechanical issues. One might think of atrial fibrillation, but on a much grander scale. Now, if that's true that Alzheimer's does have an electrophysiological component, then that suggests the neuromodulation approaches could stabilize the network and induce neuroplasticity and change the course of the disease. One of the key tools that we use in this investigation and to personalize is TMS EEG, we find that the brain with 100 volts per meter bang, and the signals reverberate across the network in a very complex signature pattern that is unique to each patient and forming the basis of our personalization algorithms. The brain is organized into multiple functional networks, the default mode network is the one that's correlated with episodic memory and Alzheimer's, its dysfunction is highly correlated with Alzheimer's progression. In fact, it's one of the earliest harbingers of Alzheimer's, the research world is starting to appreciate that there's more to Alzheimer's than just amyloid. And the dmn is our key target that we focus on the precuneus is the key target on the dmn. So building on five previous clinical studies, the landmark study we're here to discuss was a landmark 50 patient randomized, double blind, Sham controlled design in mild to moderate patients. It looked at all the gold standard endpoints that you would expect to see in a pivotal drug trial today. And the results were a complete knockout. You can't see the data on the chart, you can read the paper but on CDR some of boxes the gold standard primary endpoint that you'll see in all the drug trials today, including the Canon Mab, a 1.17 points difference from active to Sham representing an 82% reduction in the rate of decline. I'll say that again, an 82% reduction in the rate of decline, and then on Adas, cog and MMSE to other secondary cognitive endpoints. It also achieved statistical significance of the same magnitude in the 80s, in terms of reduction from the rate of decline three and a half points on Adas cog, and one and a half points on MMSE. But then on the right on activities of daily living, this is what really matters to me as a potential caregiver activities of daily living. This is the ability of a patient to feed themselves and dress themselves and bathe themselves. We achieved an eight point spread and the active arm even got just a little bit better. So just for context, this is the recently approved Locanda Mab. This is their clinical data on the same endpoint of cdr some of boxes at 18 months, they were able to achieve a point 451 separation from placebo, representing a 27% reduction in the rate of decline. So back to our study, not only do we achieve some highly statistically significant outcomes on clinical cognitive and functional endpoints, we also achieve remarkable changes in the electrophysiology of the brain and in imaging. On the left you see functional neuro functional MRIs which show that we change As the connections and strengthen the connections in the default mode network on gamma on oscillatory activity, we raise the level of gamma in the brain in the TMS arm. And then on gray matter by via structural MRI analysis, we show a reduction in the rate of atrophy in gray matter. And then on the right, on cortical excitability, we maintain the cortical excitability of the brain relative to Sham which dropped, which is exactly what you'd expect in Alzheimer's patients. All of this is very strong corroboration of what we're seeing clinically, we're changing the way the brain fires and how it's wired. All of this was published in the prestigious brain journal out of the Oxford University Press, and earned US FDA breakthrough designation. The research community is starting to really appreciate this data. And now it's our job to get this out to the world. So the patient's experience, we load the patient's MRI into our neuro navigation software, so we can see where we're going in 3d space and come back to the same spot every time repeatedly. Those are the nodes and the default mode network, you'll see the key node, the precuneus on the right in the back of the head coming into view. That's our target. It has projections, the medial PFC, the angular gyro and the parietal lobes. In a normal healthy functioning brain, you see a strong, organized signaling pattern between the nodes on the network which modulate depending on resting state or task orientation. But in a disease brain, you see a disconnection on the nodes, you see a dysregulation in the firing patterns, and the patient loses the ability to write and read memories. As I mentioned, the key step in our process involves personalization, where we fire once at the precuneus and listen to the signals reverberating around the network. All of that EEG data is fed to our cloud based personalization software algorithm, which analyzes the data in spatial temporal domains, and returns a prescription that is precise for that individual and specific for that individual in order to get maximum target recruitment, and get these wonderful results. After that calibration step, the patient comes back for weekly 25 minute sessions. And the recalibration step is repeated every few months. Now, if you're wondering if patients do come back, we had a 92% treatment compliance rate in our study, that's even in the middle of COVID. And remember, these are elderly patients. So the Sinaptica business model is we will sell the system hardware and we will also charge per use. Let's say that the cost of the system the price of our system is 200,000. That's 40,000 amortized per year, we will also charge $125 per use, each system is only capable of 2000 treatments, that's 40 patients, so 290,000 per system per year to Sinaptica. Now keep in mind, that's only 40 patients per system, out of 2.2 million in our target audience out of 4.8 million mild to moderate patients. Now let's look at our customers economics. If current reimbursement coding levels hold, they stand to make $7,379 per session, they can treat 40 patients per system. Each patient has 50 treatments per year. That's 758,000 per system per year. So as you can see, this is transformative economics for neurology practices work protected by multiple modes. We have patents filed that cover the algorithmic personalization approach that you see used here. If we're smart about reimbursement, it'll be specific to our way of personalizing the therapy. And it's taken almost a decade of developing our proprietary treatment algorithms in order to personalize the therapy and get these great results. Management has significant experience both in med tech and in biotech, including in the neuromodulation industry, and also in capital sales equipment. And we're really lucky to have the former CEO of the leading TMS company as a strategic advisor, along with their VP of r&d. We're in process on a $5 million seed to complete our clinical device development. That'll be followed by our pivotal for our Pivotal, we're thinking it's a 200 patient 12 month endpoint with a one to two year follow up after that. So as you can see, relative to a drug that would take 1000s of patients and many safety questions unanswered, we have a relatively straightforward pathway to multiple inflection points. So in summary, Sinaptica is coming out of stealth with unprecedented phase two clinical trial results that hits all four gold standard endpoints and is corroborated by electrophysiological and imaging data. We're looking for visionary investors who want to be part of this breakthrough in the disease of the century, and what could be one of the biggest markets of the century. Thanks for listening.