Ken Mariash Presents Sinaptica Therapeutics at LSI Europe '23

Transcription

Ken Mariash  0:00  
Hi I'm Ken Mariash, the CEO of Sinaptica Therapeutics, I'm here to tell you about our personalized network neuromodulation for Alzheimer's, which has achieved unprecedented phase two clinical trial results, results better than any drug that we're aware of in the disease of the century. So it just happens to be today it's world Alzheimer's Day. I don't know if they planned it that way. But Alzheimer's is a thief that robs not only the person affected, but it also totally engulfs the families of the affected in a way that no other disease does. Unlike other terminal diseases, Alzheimer's patients often require around the clock supervised care, which will often bankrupt families for years of nursing home assistance as they watch their loved one slowly fade away. This is why it's the most feared disease in American and throughout the world. It cost the direct healthcare system 300 billion or more in the United States alone, and 340 billion in direct caregiver expenses, putting it on a pathway to be the first trillion dollar disease by 2050. So, for 20 years, we've been focused on what I call the usual suspects, amyloid and tau, which are loosely correlated with the disease progression, and they plateau and yet the disease continues. The recently approved drugs like McCanna Mab and Donato Mab. They do a great job of clearing amyloid, but the disease continues relentlessly. So what if amyloid was just a covariant? And not really the cause? Well, our scientific co founders have been looking at this for over 10 years and they've been looking at other suspects that are hiding in plain view. Giacomo is the director of the Center litsea brain stimulation lab in Rome, and his partner Emiliano center. necky is at Harvard mgh. And they're looking at amyloid sorry, they're looking at Alzheimer's in a totally new way that is not obsessively focused on amyloid, they're looking at Alzheimer's, more as an electrophysiological disorder. Now, if you think about heart disease, atrial fibrillation, for example, pacemakers, that's an electrical disorder of the heart. Well, Alzheimer's could be that on a much grander scale. And just like a pacemaker stabilizes the firing patterns of the heart. That could be this except that the pacemaker actually grew new heart tissue. Because we induce neuroplasticity, we actually create new connections and the default mode network, which is our target. So this is the key tool that we use to personalize this is TMS paired with 64 channel EEG, we fire once at the precuneus in the back of the head with one pulse. And it's like dropping a pebble into the pond. We listen to the signals reverberating around the network in in 64 channel EEG. And this is the basis of how we personalize the therapy. Every patient's brain responds differently. So fundamentally, we need to personalize the therapy based on how their brain responds, where we stimulate and how we stimulate. This is our target. The default mode network is associated with episodic memory and introspection. It's actually where you integrate your memories, it's almost where the sense of self is formed. If you had to pick a place it would be this network. So the dmn is very, very correlated with Alzheimer's progression. And its dysfunction is one of the earliest signs that you have Alzheimer's, and it's more correlated with Alzheimer's progression than amyloid. It represents a perfect target for amyloid. So this was the investigation. Building on five previous clinical studies, we designed a landmark proof of concept phase two trial in 50, mild to moderate patients. First we did a TMS EEG personalization. And then we did daily induction sessions for two weeks, followed by weekly stimulation for 25 minutes out to six months, we looked at all the right endpoints that you would expect to see in a pivotal drug trial today. And the results were a profound success. This is unprecedented data that has never been seen by any drug, at least that we're aware of. On the primary endpoint CDR sama box is a gold standard cognitive and partially functional endpoint. We slowed the disease of Alzheimer's by 82%. And then on Adas cog in MMSE, which are also two other endpoints associated with cognition, over 80% slowing of Alzheimer's disease. On the right is ADLs. On ADLs we actually arrested the progression of the disease 100% slowing, you never see that in pharmacy studies today. ADLs is what really matters. This is the difference between my mother needing a nursing home or me keeping her in her own home. So this is for context. This is the latest drug Locanda Mab on the same endpoint CDR sama boxes at 18 months with bi weekly IV infusions, they were able to slow the disease by 27%. A difference of less than half a point on CDR some of boxes, clinicians will tell you they can't even tell the difference between a PE shunt with less than half a point on CDR sama boxes so it works but only barely and also carries 12% rate of brain bleeding and swelling. So let's come back to our study. You may wonder, that's great that you changed cognition and function. But did you actually change the brain? The answer is absolutely we did, we changed how the brain is firing. On the left you see measures of gamma oscillatory activity in the brain. In the TMS arm, we raise the level of gamma, which is associated with plasticity and a healthy brain function in the SHAMET dropped. On the right are measures of evoked potentials. Those are those graphs that I showed you earlier that show the propagation of a signal from one single pulse. It was unchanged at six months in the TMS arm, and it dropped in a sham arm. Also on imaging, remarkable corroboration that what we're seeing clinically is backed by real changes in the brain. On the left is fMRI. We showed more connections were created in the precuneus, where we're stimulating in the middle you see microstructure as measured by this variable called angle R, we can see that we preserve the microstructure of the brain. And then on the right, you see atrophy levels, we were able to slow the rate of atrophy in the brain, remarkable corroboration, that we're actually changing the brain with our stimulation. This earned US FDA breakthrough designation. We were published in the Oxford journal Brain. And now finally, having presented these data from the podium at AIC, we're getting breathless press. OK, here's our system, we're going to sell the entire system. And we're also going to charge per use. Rather than walk you through the steps graphically, I'm just going to let this video kind of bring it all to life how the system works. So first, we load the patient's MRI into our neuro navigation system. So we can see exactly where we're going in 3d space, see exactly where we're about to stimulate on that patient's brain. The nodes of the default mode network, as you see are interconnected. And we're aiming for the precuneus, which is a rather large structure in the back of the head coming into view. In a normal brain, there's an organized signaling pattern between the nodes and the network that modulates Despit, depending on resting state or task orientation. But in an Alzheimer's patient, the signaling becomes disorganized, and dysregulated. Almost like atrial fibrillation, as I said before, the nodes become disconnected and the patient loses the ability to read and write memories. As I mentioned before, we have a personalization step where we fire once at the precuneus. And we listen to the signals reverberating around the network through 64 channel EEG, that generates a ton of information that we processed in the cloud with our cloud based personalization engine that analyzes the signals in order to determine where to stimulate and how to stimulate for that particular patient. Fundamentally, we believe that this personalization is critical to getting the right engagement and the right resonance of the default mode network to achieve these great results. The patient then comes back every week for weekly maintenance sessions. And we had 94% compliance in our phase two, even in the middle of COVID. Economics we'll sell the system for say 200,000 over five years, that's 40k Charge 125 per use systems can do about 2000 treatments in a year. That's 290,000 per system per year to synaptic. And keep in mind that's only 40 patients of the 2.2 million in our target. The economics for our customers are even better. If current reimbursement levels hold for TMS for depression, plus an E G code plus or neuro navigation code, roughly it's 379 per treatment that goes to the neurologist. They can do about 50 treatments per patient that's 40 patients at 750,000 per system per year. They have to turn around and pay us the 250 per use fee higher technician and the amortized cost of the system. You can do the math. It is transformative economics for neurologists, whereas they only make about 50 bucks on the Locanda Mab infusion. We have modes protecting our intellectual property. It's based on our proprietary algorithms. And the team including myself has a long history in capital equipment neuromodulation biotech and the TMS space. We recently hired a VP of Clinical he's actually just run a pivotal study in Alzheimer's with neuromodulation. We are just closing we're happy to announce we closed our seed round well oversubscribed. We are in process on 36 million. That'll take us all the way to FDA clearance that builds software hardware and 20 clinic clinical units for the pivotal study. So in summary, this is unprecedented data in the disease of the century. And we're looking for visionary investors who want to be part of this big breakthrough. Thanks very much.