Emiliano Santarnecchi, Sinaptica Therapeutics - Spotlight Interview | LSI Europe '23

Sinaptica Therapeutics is a clinical-stage company that is developing a personalized closed-loop neuromodulation therapy for Alzheimer’s Disease.
Emiliano Santarnecchi
Emiliano Santarnecchi
Co-Founder & Scientific Advisor, Sinaptica Therapeutics



Nick Talamantes  0:17  
I'm here at LSI Europe in Barcelona with Emiliano Santarnecchi of Sinaptica Therapeutics Emiliano, thank you for joining me in the studio.

Emiliano Santarnecchi  0:25  
Thank you for the invitation.

Nick Talamantes  0:26  
Tell me a little bit about yourself.

Emiliano Santarnecchi  0:28  
Yeah, start from my origin. I was born and raised in Tuscany in Italy. But for the vast majority of the last decade, I spent my life in Boston in the US. I'm a professor of neuroscience. And I'm gonna go into the details, but professor of neuroscience at Harvard Medical School at Harvard University, in a run in the right neuromodulation program at Mass General Hospital in Boston. 

Nick Talamantes  0:50  
So how does a professor of neuroscience find his way into a startup company?

Emiliano Santarnecchi  0:55  
That's, that's a great question. I've got to be very honest, like doing this job for now 15 years. And living in Boston, you get approached many times by companies that are they want you to be an advisor, or one just to talk with you for an hour, or want you to join the company or start the company, whatever the idea is, that is this kind of nice, incubator feeling in Boston. And I've been always skeptical about jumping into what I used to call the dark side, from academia. But you need to be lucky. And so a few years ago, I met fantastic people, which are now our co founders also in Sinaptica. And at the same time, we got this fantastic face to data. And I was put in front of a dilemma, do I keep doing what I do? I think well, but for my opinion, is going to be too slow, which means to an academic work. So with this data, we can apply for another grant, get funding, run another trial, and maybe 15 years from now, we will maybe give this to patients. And then the option was to turn this into actually private venture that maybe in two or three years could be on the market. And that was the decision. And I'm not regretting one moment that we decided to incorporate a company and here we are with practice designation in just two years. And things are really going well. I'm really here to help patients. So I funded this new channel to put my energy into, and it's going really well. 

Nick Talamantes  2:12  
Why don't you tell me a little bit about the technology that brought you over to the dark side? 

Emiliano Santarnecchi  2:16  
Yeah, so in my program at MGH we tried to really be multimodal, and when I was recruited at MGH was really to bring a program that will be multidisciplinary across radiology, neurology, and psychiatry. And I have a bit of a background in all these disciplines. And so the idea is, let's use all the data we can from the brain, but also with sensor that we can put on the body to personalize treatments and also identify novel biomarkers, but to study the brain, but also to develop new therapeutics for patients. And so what we do every day, we do multimodal imaging every way of scanning the brain we can think of, we combine that with every possible data we can use from sensors from like something like a Fitbit or an Apple Watch to sensor plays on your head like electroencephalography. And then when we have a nice model of your brain, we start looking at what is the best way to modulate this brain. So we tried to create digital twins of the brain. And that gave us two options. One is to sometimes avoid actually testing things on the actual brain of a patient's or an individual because we can run mathematical simulation and see kind of predict where the brain is gonna go. If I add this intervention being a drug or brain stimulation, and at the same time, it can suggest us really what is the best spot to target in that particular brain. And that's what convinced me that this needs to be intubated into a company because it's getting too complex, we need proper funding to really bring it to millions, so people and not just a few patients every year. 

Nick Talamantes  3:40  
So there are really two arms, then to synaptic, or therapeutics, you have this digital twin, that allows you to run simulations on how your therapy will affect the patient without actually testing them. And then there's the technology itself. Before we jump over and talk a bit about the technology that the therapeutic side of it. I'm curious, it sounds like you're working with a ton of data based off of what you're telling me. How are you guys managing all of that data? Is there an artificial intelligence component to it all? 

Emiliano Santarnecchi  4:06  
Yes, and that word is inflated. And now like everybody use it, but we will be using it more than a decade ago, at the time was machine learning, then it became deep learning. Now it's a bit more sophisticated because it's really grounded into neurophysiology. So we don't just run a mathematical model on data for we have actually mapped out part of the circuitry of the brain that generated data in a real brain. And so when we have the sit with to figure it out, we can really simulate it with some AI component. In that we try to solve the puzzle with data and mathematical model that makes predictions.

Nick Talamantes  4:38  
So you're modeling the patient in advance using a combination of AI and sophisticated software. How are you actually treating the patient? 

Emiliano Santarnecchi  4:48  
So once we have defined the target and the target means both where to stimulate but also the intensity? Sometimes the frequency, it's a combination of factors. We then deliver the therapy in this case for synaptic once every week, when we basically took the brain for around 20 minutes by sending magnetic pulses, that when reach the brain turns into electricity, and the basically activate neurons in the brain, and you do that kind of repetitive stimulation for about 20 minutes. And we know from animal studies from now three decades ago, and also from studies from our group, that this type of repetitive stimulation, induce effects that outlast the stimulation period, so you don't just change the brain while you're stimulating. But when you stop stimulating the brain retain some of those changes. So you induce brain plasticity. And that's what we leverage, we just do it once a week for 20 minutes. But the effect in our study shows that if you keep doing it once a week, for months, the effect last, and we try to induce a change in the brain that way.

Nick Talamantes  5:43  
Alzheimer's Disease is a progressive disease where you see a slow and then in some cases rapid decline in cognitive function. How effective is your therapy in reducing or stopping that decline? 

Emiliano Santarnecchi  5:58  
Now we get into an area where it's difficult to make an estimate, because we need proper data like from people to where we can stimulate for longer. But what we have seen so far is that, for instance, our data is six months show that in terms of functionality and activities of daily living, meaning how independent the patient is, there was no change in that regarding the patient that received real stimulation, while there was a significant drop in the group that received placebo. We have some extension data one year and the pattern seems too old. So the idea is that you keep the disease at bay, the symptomatology doesn't progress. Ideally, you could keep the patients in the same spot for a couple of years, maybe more depending on where they started. And the goal, obviously, for us, was to start in mild to moderate Alzheimer's disease, because that's where usually, you start planning to attack Alzheimer disease, because you want to see an effect in patients that already have kind of a significant symptomatology. But our goal is to then go earlier and earlier, and to help constipation when I get the first signs of the disease.

Nick Talamantes  6:51  
So Emiliano, tell me a little bit about what advantages you get when you are able to personalize therapy to the degree that your technology is able to do so. 

Emiliano Santarnecchi  7:02  
Yeah, I think precision, which by the way, is the name of my program at the hospital is precision neuroscience and neuro modulation program, is the idea that now we know by having more data that every brain is different. I think we all knew, like since the dawn of time, that every individual is different, everybody thinks about things differently. But now with access to the data and some modeling that we comment on before, we really know that every brain is different, not only in the way it fluctuates spontaneously during the day, but also in the way response to stimulation. And so over the years, we have invented what I like to call perturbation based approaches, but to measure the brain and to change the brain. So we discovered that and this is been known in mathematics and physics for many, many years. That when you try to measure a complex system is way easier to understand, really that system if you send the perturbation, and then you look at how the system responds to the signal, then just looking at what the system than passively. And that applies to the brain very well, because the brain at the end is the most complex system of the universe, each one of us has a very complex system in their head. And so we discovered them, the minister magnetic pulses, and then you listen to what the brain does, you get very, very specific information is almost a fingerprint of that individual. And when you have that now, you can really understand how the individual would respond to any type of repetitive stimulation. And so we do that for each individual at the beginning of the therapy, you do one session, when you put an EEG cap on, we stimulate with magnetic pulses, we look at different parts of the brain to really find that sweet spot to give us activation where we want it and will make the entire network resonate. The other crucial component is that in this field, now we are moving towards network neuroscience, unfortunately, for many years, and that's understandable, because it was the beginning of brain stimulation. But for many years, we kept focusing on specific regions, like we were thinking that the solution will be interesting Region One regions, the same for everybody. And it was it was kind of a dream that it would work. And sometimes it did. But in the last 10 years, we really understand that the brain works at a combination of networks. Now you need to find the right one. And you need to know where to stimulate that network to make it resonate. And that's the other advantage of synaptic therapeutics, we really go after one specific method that we know it's very relevant for Alzheimer's disease, and it's called the default mode network. And that's the network that basically control your memory just to make it very simple. And not by accident is the first network that drops in the Alzheimer brain even 15 years before diagnosis. And so to find the right network, but not only that, find it in the right position in each brain to really engage the network is crucial to do with the right dose, the right intensity. It's even more fundamental, and that's why we do everything we do to really personalize the therapy.

Nick Talamantes  9:40  
It's fascinating. Emiliano I want to thank you for stopping by the studio and telling me about what you guys are doing Sinaptica Therapeutics.

Emiliano Santarnecchi  9:46  
Thank you. It's been a pleasure.

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