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How AI Is Creating an Inflection Point in Brain Health Innovation: Reporting from the AAIC · StartUp Health NOW Podcast

• 0:00
  Welcome back to Startup Health Now, the podcast where we celebrate the entrepreneurs and the innovators who are transforming health. I'm Logan Plaster.
• 0:08
  [gentle music] This week, the Startup Health team was in Philadelphia at the Alzheimer's Association International Conference, AAIC.
• 0:16
  We brought together our Alzheimer's moonshot community and got to see the magic of convening a room full of passionate, collaborative founders.
• 0:24
  It never ceases to amaze me what is possible when founders working toward a common mission, like ending Alzheimer's, lower their guard and make collaboration a priority.
• 0:34
  While I was in Philly, I interviewed about a dozen of the founders from our community and got their latest updates.
• 0:41
  I wanna share two of those conversations with you today on this episode because they're indicative of a broader trend that emerged from the day of conversations. The trend?
• 0:50
  That Alzheimer's disease is at an incredibly unique inflection point because technologies like AI and machine learning are allowing us to process data from the brain, the signals coming off the brain, in a way that was previously impossible.
• 1:04
  That's leading to a new multimodal understanding of the brain that has the potential to revolutionize how we think about all brain conditions, not just Alzheimer's.
• 1:15
  To add detail to this topic, we'll start with my conversation with Katherine Bornebaum, Chief Business Officer at RetiSpec.
• 1:21
  RetiSpec just closed a $10 million round in support of their device, which uses AI to analyze the retina in the eye, getting a glimpse into brain health through the window of the eye.
• 1:33
  Here's Katherine interviewed on the streets of Philadelphia outside of AAIC. [upbeat music] Katherine, great to see you. Great to see you, too. RetiSpec recently joined the Alzheimer's moonshot at Startup Health. Yes.
• 1:46
  And you did so at a very exciting time. You just raised $10 million. Yes. So tell me a little bit about that raise. Oh, my goodness.
• 1:53
  Uh, following 2023, which was a, a bit of a tough landscape in the, uh, fundraising era, um, we are very, very fortunate to have just recently closed 10 million USD, and this was a round that was led by iGan Partners, who is a group that really focuses on med tech innovation, um, and particularly in Alzheimer's disease, so we're very fortunate.
• 2:14
  Um, and we have some new strategic investors that we are very, very honored- I'd heard about that. Yes. Um, we're honored to be working with them. Who are they? Uh, Eli Lilly. Okay.
• 2:23
  Uh, the Lilly Ventures arm of the company, and they are just making waves in the Alzheimer's and neuroscience space, so we are delighted- Okay... to have them, uh, alongside us. And also a group called Topcon Healthcare.
• 2:35
  Yes.
• 2:35
  And so this is the company that, they are one of the most significant, uh, manufacturers of fundus cameras, which are cameras that take a picture of the back of the eye, which is what we actually use in order to understand what's happening within the body, and in particularly in the brain.
• 2:50
  Okay. So speaking of fundus cameras, I know RetiSpec is a special kind of camera that sits on top of a typical eye exam camera- Yep... fundoscope. Yeah. Exactly. Um, what's the...
• 3:02
  What are some of the challenges and opportunities with working, trying to come to market, working with eye doctors, primary care physicians, and trying to add technology onto existing technology?
• 3:13
  Yeah, so there's a couple things to unpack there. So I think first of all, the fact that we use cameras that are already widely available in eye doctor's offices is a big strength.
• 3:21
  Um, what we do with that is by adding the extra information on top, we get that little sensor, and we can capture extra data.
• 3:28
  Uh, and we build deep learning models in order to detect signs of what's happening in the brain, in particular, uh, with Alzheimer's disease.
• 3:34
  And so what we do is we just simply swap out the camera, do a calibration, and they're ready to go. It's really, really simple. Um, what you're asking is about really what happens after that. Yeah.
• 3:44
  After you swap out the camera and the software's ready to roll, how do you work with clinicians to make sure that they're ready to deliver this information?
• 3:51
  And we actually were quite concerned about how we might, uh, integrate this into clinics, and so we did a couple pilots.
• 3:57
  Uh, one was sponsored by the Davos Alzheimer's Collaborative, where we actually put our cameras in optometry offices. We invited folks who were above a certain age, in our case 55,
• 4:07
  um, to see if they were interested in having a scan. And what we found is that it was really, really much easier than we thought. Ooh.
• 4:13
  Um, the optometrists were excited to talk to their patients about brain health, and we didn't realize that they actually do that every day. Hmm.
• 4:20
  They look for signs of stroke, of brain tumors, and they have these conversations [siren sound] with their patients every day. So it wasn't completely new. Um, we were just expanding on that scope of practice.
• 4:29
  Um, and so following that Davos study, we actually followed what happened to these people. Did they go to primary care? Did they go to a dementia specialist, if that was relevant? And actually, in all cases, they did.
• 4:38
  They followed up with primary care when relevant. Um, and if they couldn't, then we helped connect the dots for them, um, to a nurse practitioner who could have the conversation, so.
• 4:47
  Now, obviously, it's, it's awesome to have, you know, greater access to brain health scanning at a primary care doctor. Uh, is this a big capital investment?
• 4:56
  Is this gonna be a big hurdle for, let's say, a small town eye doctor or physician to do? That's a great question. So the short answer is no. Um, we're not asking folks to buy a really expensive piece of equipment.
• 5:08
  In many cases, they already have the fundus camera, so we're just adding the sensor on top. Um, but we roll this into a really affordable subscription model for folks. Oh, okay. Okay. So they're very familiar with this.
• 5:17
  Uh, in eye care, they already do a lot of these, um, purchasing, uh, agreements through, um, subscriptions or, um, they just go along- Yeah...
• 5:25
  with the cameras that they already buy, so it's a very familiar, uh, business model for these folks. Okay. Okay. Yeah. What are you most excited about what you're seeing at AAIC? Oh, my goodness.
• 5:32
  Um, it is such a heartening time in Alzheimer's disease. Okay.
• 5:36
  We have just had the approval of the new Eli Lilly drug, uh, Kisunla, and we are seeing some exciting, uh, top-line data coming out of some other companies, like Alzeon, uh, very soon.
• 5:46
  So I, I think there's huge innovation happening on the diagnostic space, the therapeutic space, and even in some of the complementary areas.
• 5:53
  So some of the startup health companies, um, that we're seeing innovation across the continuum, from the caregiving experience through to, um-Supportive videos.
• 6:02
  I think there's, there's just innovation everywhere- Yeah... and I'm so excited. Is that new, or are we just sort of seeing it now? Like, is there actually an inflection point happening in innovation in Alzheimer's?
• 6:13
  I think absolutely yes. Uh, I think a lot of it is driven by the success of the therapeutics after 40 years of failure.
• 6:18
  But there's so much energy and, um, focus on, okay, now that we have options on the therapeutic side, how do we support the rest of the ecosystem- Mm...
• 6:27
  for patients, for families, um, and everyone involved in their care? So I think there's a lot of energy coming out right now, and we are just very excited to be a part of it.
• 6:36
  What should we be looking forward to from RetiSpec over the next 12 months? Oh, so with the, with the close of our round, we are looking forward, uh, to some significant milestones.
• 6:44
  So we'll be gearing up for regulatory and all of the efforts that go into that and getting ready to bring this out to clinic, so. Amazing. Yeah. Amazing. It's a really exciting time. All right.
• 6:52
  Katherine, I wish you the best. Thank you very much, Duncan. All right, [laughs] thanks. Thank you. [upbeat music] Next up, let's jump into my conversation with Ken Marash, CEO of Synaptica.
• 7:04
  This company is working with some of the top neuroscientists in the world to discover new ways to use AI and neuromodulation, a form of electrical brain stimulation, to slow the progression of Alzheimer's.
• 7:17
  Their initial results have been really incredible, as you'll hear, and it just opens a new door for how we can not only delay brain degeneration, but actually strengthen the brain and improve memory in healthy subjects as well.
• 7:30
  Here's Ken explaining what he's building at Synaptica, recorded outside of AAIC in Philadelphia. It's a non-drug, personalized neuromodulation approach.
• 7:41
  We're stimulating a region of the brain that's associated with episodic memory- Okay... which is strongly implicated in Alzheimer's, and we do that in a really personalized way.
• 7:50
  So we find the right spot on the brain for every patient that gets the right engagement of the networks that are related to memory. Okay.
• 7:58
  And we have published peer-reviewed phase II data that is unprecedented, showing 82% slowing of the disease of Alzheimer's in mild to moderate patients and over 80% on all other re-re-relevant secondary endpoints. 82%.
• 8:12
  That's, that's... Those are high numbers. They are unprecedented. How has the industry responded to this research? Uh, with excitement and also with, um, surprise- Yeah...
• 8:24
  because nobody thought that a neuromodulation approach could, uh, induce such remarkable changes in the brain. You know, we just published imaging data that shows that we do just that.
• 8:36
  Our stimulation therapy literally remodels the brain on the micro, macro, and connectome levels.
• 8:42
  We're literally remodeling the brain and building new connections in the f- in the functional networks that are associated with memory.
• 8:49
  What have been some of the challenges associated with advances in neuromodulation up to this point? I, it's a, it's a field, um, that maybe has, like, struggled to get acceptance. Is that fair to say?
• 9:02
  You know, in many areas of medicine, neuromodulation has really disrupted various disease states. It's a major industry. It's a $7 billion industry. So Parkinson's, for example, well established.
• 9:13
  Spinal cord stimulation for pain, very well established. Uh, sleep apnea, overactive bladder. I could go on. Yeah.
• 9:19
  There's lots of different ways where neuromodulation is displacing or working with existing drugs, and so we see this as no different. We know that neuromodulation induces neuroplasticity in the brain.
• 9:30
  The question is getting it into the right spot. Okay. And so you asked about struggles with neuromodulation. The struggles have been with precision and lack of personalization.
• 9:39
  So lack of precision, lack of personalization. We bring both of those to the table. So where you stimulate, turns out, [laughs] really matters in the brain. Yeah.
• 9:46
  Everybody's brain responds differently, so personalizing the stimulation to hit your networks that are related to memory and not some other network related to, say, attention or the salience network or the language network or the visual network.
• 9:59
  We need to hit the right network, and so the, the location and the intensity of the stimulation needs to be specif- specific for each individual. Okay.
• 10:07
  Let's talk about some of the interesting opportunities and challenges related to going to market with a device. You actually have to do the neurostimulation in an office.
• 10:17
  So talk to me about kind of where you envision people getting this care and what that looks like. Is it every day, every week, every month? How do you do it? Yeah.
• 10:24
  So the drugs like lecanemab and donanemab are infused already, so the patient already has to come in for a 90-minute infusion every two weeks, for example, with lecanemab.
• 10:33
  With our therapy, it's a 20-minute painless stimulation session in a doctor's office. And so it does involve training the staff on how to use the machine. It's not that complicated. Yeah. It's similar to an MRI tech.
• 10:44
  Uh, TMS for depression is a very well-established therapy. Uh, something like 40,000 patients get TMS therapy for depression every year.
• 10:52
  And so we're, we're building on an infrastructure and an awareness and a safety record that's already there. So it's not a challenge that hasn't been surmounted in other areas of medicine.
• 11:02
  We know that TMS works in depression. The question is, can it also work in this disease state? And so far, with the phase II data from two phase IIs that we have, so far the results are really, uh, really promising.
• 11:13
  Obviously, we're here at AAIC. Any responses here from the research that you're presenting? Lot of excitement on this imaging paper. Yeah, because what it shows is...
• 11:23
  And you might ask the question, it's a good question, which would be, are you just giving patients a temporary boost? Mm.
• 11:29
  You know, like a, a caffeine boost or a sugar high to spike the levels of cognition and function in the brain, and we're not doing that. We're actually remodeling the brain.
• 11:38
  We're seeing s- true evidence of neuroplasticity in the brain. We see with fMRI new connections built in the brain. Wow. We see with structural MRI we're preserving gray matter.
• 11:47
  At a micro level, we show that we're preserving the columns, the mini-column structure- Wow... the architecture of the brain.
• 11:53
  So we're literally remodeling the brain, similar to, you know, for example, remodeling the heart in heart failure or heart disease. Where do you see this going? Because I wanna remodel my brain. Sure.
• 12:04
  I feel like I'm, I'm forgetting things. Like, where does this go beyond Alzheimer's? Uh, it's gonna go up to MCI. Okay. So get to patients earlier.
• 12:12
  Why would you wait until you had stage III cancer before you treat it, right? Yeah. We wanna get to patients before they have, uh, symptomology that's too advanced. And then beyond that, who knows?
• 12:22
  We could go into many disease states other than Alzheimer's. Anything neurodegenerative, in fact, anything involving a circuit in the brain that we need to probe, that's a disease state we could go after.
• 12:32
  You know, the fundamental technology that we use is TMS, but it's also paired with EEG. Uh-huh. And so what we do is we ping the brain with single pulses. It's like active sonar of the brain.
• 12:41
  That reveals so much about the connectome- Yeah... in your brain, how the different nodes of your brain are connected. Yeah.
• 12:47
  When you pulse the brain, it's like dropping a pebble into the pond and it reveals the, uh, the topology of the pond, so to speak. Wow.
• 12:54
  So we know that we're hitting the right targets when we do that TMS EEG, but it generates a barrage of data, a huge amount of data that we need to parse, and we know how to do that.
• 13:03
  We've built the algorithms that enable us to parse that data to know that we're hitting the right target and not the wrong target. Right. So it is a data aspect, too. Yeah. Yeah. Yeah.
• 13:12
  Which, which sort of means we've come to this moment, now we're ready for this kind of innovation because we have the ability to crunch that data. Yes, we do, ML. We have the tools. Yeah, exactly. So, uh, last question.
• 13:22
  What's, what are you looking forward to most? What should we be looking forward to from Synaptica this year? Uh, y- you should be setting your calendar.
• 13:29
  October 31st in Madrid at the CTAD conference, we will present data from our second phase II- Wow... with a one-year endpoint. And I can't tell you too much about it, but it's gonna be very exciting data. That's cool.
• 13:41
  Okay. Okay. We'll be looking for it. So mark your calendars. [laughs] Okay. [laughs] Thanks. Thanks, Ken. All right. Hope, hope it's a great conference. Good to see you. All right. Thanks so much.
• 13:46
  [upbeat music] Thanks for listening to Starter Health Now. We'll be back again with another episode next week. [upbeat music]