Akili built A Video Game to Help Kids with ADHD

 

Can a video game help improve attention skills in kids with ADHD? According to Akili Interactive in Boston, the answer is yes. They’ve created an action game called EndeavorRx that runs on a tablet and uses adaptive AI  to help improve focus, attentional control, and multitasking skills in kids aged 8 to 12. And it’s not just Akili saying that: In 2020 the U.S. Food and Drug Administration agrees cleared EndeavorRx as a prescription treatment for ADHD, based on positive data from a randomized, controlled study of more than 600 children with the disorder. It was the first video game ever approved as a prescription treatment for any medical problem, and Harry’s guest this week, Akili co-founder and CEO Eddie Martucci, says  it opens the way for a new wave of so-called digital therapeutics. Even as Akili works to tell the world about EndeavorRx and get more doctors to prescribe the game for kids with ADHD (and more insurance companies to pay for it), it’s testing whether its approach can help to treat other forms of cognitive dysfunction, including depression, the cognitive side effects of multiple sclerosis, and even Covid-19 brain fog.

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Transcript

Harry Glorikian: Hello. I’m Harry Glorikian, and this is The Harry Glorikian Show, where we explore how technology is changing everything we know about healthcare.

Can a video game help improve attention skills in kids with ADHD?

According to Akili Interactive in Boston, the answer is yes.

They’ve created an action game called EndeavorRx that runs on a tablet and uses adaptive AI  to help improve focus, attentional control, and multitasking skills in kids aged 8 to 12.

And it’s not just Akili saying that.

The U.S. Food and Drug Administration agrees.

In 2020 the FDA cleared EndeavorRx as a prescription treatment for ADHD, based on positive data from a randomized, controlled study of more than 600 children with the disorder.

It’s the first video game ever approved as a prescription treatment for any medical problem.

Kids are advised to play the game for 25 minutes a day, five days a week. After two months of play, two-thirds of parents of kids in the controlled study said they saw a meaningful change in their children’s day-to-day impairments.

The FDA’s approval of EndeavorRx opens the way for a new wave of so-called digital therapeutics, designed to treat all kinds of problems with cognitive functioning, including depression, the cognitive side effects of multiple sclerosis, and even Covid-19 brain fog.

Akili is busy telling the world about EndeavorRx and working to get more doctors to prescribe the game for kids with ADHD and more insurance companies to pay for it. And here today to tell us about all of that is Akili’s co-founder and CEO Eddie Martucci.

Harry Glorikian: Eddie, welcome to the show.

Eddie Martucci: Thanks, Harry.

Harry Glorikian: So I’m dying to get into the company and all the things you guys are doing. But, like, before we jump into the company, I’d love our audience to get to know you a little bit. Right, because you’re a long time health entrepreneur. You got your PhD at Yale in the departments of pharmacology and molecular biophysics and biochemistry, where you studied structure based drug design. But how did your personal path lead you from molecular biology, which is near and dear to my heart, to video games to treat cognitive impairment? I mean, that that’s not exactly the Venn diagram I would see that somebody would just put together.

Eddie Martucci: No, it’s not. And there is no there is no path for this. Right. Because this is so different and so new. I would say my personal passion is just new science findings. Like I just love brand new science. I was a researcher for a short stint while I did a PhD. I think I had some pretty cool research. But really, if I zoom back, it’s new science and new discoveries that are moving the health world forward. And that can be whether it’s insights about some part of our biology that we didn’t know before, that leads us to understand the human body better. Or in the case of what I’ve really done from a professional perspective, it’s scientific insights that can lead to new treatment modalities. And so that’s really what got me most excited. I think the path that was most impactful for me, you know, I was a biochemist at Providence College and a biochemist and biophysicist at Yale, and I love proteins and structural biology and all that. I still do. But I came out of my PhD and and worked with a group called PureTech Health in Boston. And Puretech is really just this unique new health care company where they’ve done everything from, they have research and development and discovery, but they also have in many ways nailed down a process of starting new companies off of groundbreaking science. And so while I was in grad school, I was exposed to a couple entrepreneurs that really put a light bulb in my head that, wow, this is something I should look into. And then I got training at PureTech in Boston. And that’s what kind of got me thinking about brand new medicine and brand new modalities that were never considered medicine before. And the rest is history. Once you get a framework where you can start thinking like that, then it’s just work.

Harry Glorikian: Yeah. I mean, I knew Daphne, I think when she started PureTech and her advisory board was like, I mean, Nobel Prize winning, who’s who sort of. Right. Just watched it evolve over time. But, you know, when you were at PureTech, I think one of their focuses was neurophysiological disorders. I mean, is that the real bridge that helped start Akili? Because I remember that came out of Adam Gazzaley’s lab at UCSF, if I remember correctly.

Eddie Martucci: Yeah. Adam Gazzaley is where we found the core technology that which we call SSME, which has gone on to power our products, including our FDA approved product. But yes, what I was working on at PureTech, including directly with Daphne, who’s really brilliant in helping and bringing new big ideas to life and board members, including people like Ben Shapiro, who used to be at Merck. And he was one of my longest term board members. It doesn’t hurt to have folks like Bob Langer in the room once every quarter to bounce ideas off of as well. So like, a very privileged place to start a company. But yes, I was working on novel CNS technologies, in fact. In fact I was working on a few and one in particular that was new devices, new devices for various neurological conditions. And it was really from that effort in thinking about what are the newest modalities of medical devices that we leaped one big bridge further and said in 2010 or about or maybe 2009, could we go further from a user experience perspective now that the whole world is carrying cell phones and tablets every day? Could we go further? Could we could we think about digital? And that was right around the time when everyone and their mother was talking about digital helping medicine. And because we were in the headspace of novel therapeutic modalities, I think it was a natural leap to say, what about digital being the medicine? And then we had to find the science. And that’s where I found Adam Gazzaley and, and, and we got off to the races with that technology from UCSF.

Harry Glorikian: Yeah. I mean this whole area of digital therapeutics, I’ve been talking about it for years now and trying to convince people and they look at me really weird when I say digital therapeutics and I try to explain it to them. But so but the game you have built is called EndeavorRx. If I got that correctly. And can you tell? Me more about the game itself. Like, what are the operative features or game mechanics that are thought to increase attention in kids who play the game?

Eddie Martucci: You kind of have to back up to the core technology. So the way we build the business is not building one product or one game. We’re building a platform technology, meaning a technology that is not made for a single disorder. But instead the problem we’re going after and that we started with all of those years ago, about a decade ago, is cognitive functioning. Cognitive dysfunction in medicine is not targeted well by molecular pharmacology. That is the problem statement. We don’t target cognition very well in medicine, if at all. And so our whole theory and thesis for the business was, if we could bring in the best technologies in the world, that through software could actually target cognitive functioning directly, then we would be bringing a pillar of medicine that does something much, much different than what medicine does today. So the technology out of UCSF that we started the company around, that we have branded the Selective Stimulus Management Engine, the way this technology works, which will then help you understand how the products in for ADHD children works. The way this technology works is it is giving constant stimulus, both visual and motor. So it’s creating conflicting and overwhelming stimulus to activate the part of the brain that controls attention, which is the midline prefrontal cortex. So the front part of the brain that really controls attention and speed of processing and integration, this technology is patented to be able to activate that part of the brain very strongly, but also enhance what’s called long range coherence. So as you’re using this technology, not only is the front part of the brain activating much more, so you can apply your attention downwards.

Eddie Martucci: And I’ll get to exactly how this manifests, I promise. It is also more seamlessly based on the neurological data we have. It appears to more seamlessly be helping the brain communicate to the sensory processing regions. And so the way this manifests in ADHD children, when they’re using our product EndeavorRx, which is meant for children 8 to 12 years old with ADHD who struggle with the attentional issues. This product is basically experienced like a racing video game where children are running a little alien figure down a course that is ever adapting. And they’re getting information, meaning things that fly up to the screen that they have to make decisions on. And that’s ever adapting because we have these deep, personalized algorithms so that everyone gets their own experience. So basically what people feel is they’re using this technology that feels like a game, and it’s just constantly challenging them in different ways. What’s happening in the brain and this is how it’s designed, is that the game is presenting very specific stimuli for each user that is pushing them at the edge of their processing ability. And that’s part of the IP we have, is how to do that in a really seamless way so that by the end of using a game you haven’t just been using a game, you have been essentially taxing the weak link in your attentional processing every single second for hours.

Harry Glorikian: I think every CEO of that we may know mutually needs to be prescribed this game.

Eddie Martucci: You know, CEOs and investors have been probably the most common people that in meetings will stop me and say, hey, I think I need this.

Harry Glorikian: Yes. So how did you ideate and test the game mechanics?

Eddie Martucci: Yeah. This is this is really a tenet of the business where we decided early on that to truly—we want to disrupt medicine and we want to create and integrate our type of medicine into mainstream medicine. Far too often, digital is kind of left to early adopters or on the sidelines of real medicine, excuse me. And our whole thesis was you have to run real validated and literally gold standard, rigorous clinical research. So when we had done this, no one had done a well designed trial before to study something that looks like a video game. And so that’s really where we spent the first handful of years of our existence is after we built the kind of data infrastructure, which we can talk about, and the adaptive algorithms. We then invested years in how to run good clinical trials with this type of product that’s an experiential product. So our goal all along was being able to run the same or better rigor of randomized controlled trials that you’d expect from a drug for this same disease area. Obviously, as an interactive product that you can see and you interact with, that means you have to take a little bit of a different approach.

Eddie Martucci: So we had to do a lot of work with some of our advisors and with places like Duke University on how to blind the protocol. Because it has to blind very differently. And how to how to have a control, an active controller sham that is actually controlled. And there’s many nuances like that. But at the end of the day, the trials we run are meant to replicate or be analogous to drug trials, where you have really strong controls up front, that you’re not biasing individuals and that the outcomes—and this is the differentiator in digital—that the outcomes are gold standard accepted outcomes for whatever you’re studying. And so that was what we’ve done. What we did the first time we were in a trial, we were like, it took a lot of work and we were nervous about it. But we have a clinical ops team now and we’ve run a few dozen trials across, I think, nine or ten disease populations, so we’ve become pretty good at it.

Harry Glorikian: Yeah, I was going to say, I mean, coming up with the first one, everybody’s probably scratching their head trying to figure out, are we doing the right thing? But, and I have this discussion with some of the people I work with all the time, what’s the proprietary special sauce in the case of digital therapy? I mean, is there a defensible algorithm or insight at the heart of something like EndeavorRx that would be comparable to a patented small molecule in the you know, in the traditional drug industry?

Eddie Martucci: In our case, yes. And I’ll tell you about that. I think what this really comes down to, though, that question about digital therapeutics, it’s like a business question for the industry. To answer that question, it’s important to recognize there’s nuance in the industry. So the vast majority of digital approaches, I think, are tough to protect because they’re taking well known human practices and putting them into an app. Right. So there’s 90 percent of the digital therapy companies or products out there are using different forms of behavioral therapy or disease management techniques or strategies, and they’re bringing them into an app that is not bad. It’s hopefully very, very good for patients. There’s a few validated products there that are, no question, good for patients. I think it does make those types of products harder to protect. We’ve taken a bit of a different tack. We’re a little bit, I guess, iconoclastic within the industry in that what gets us excited is software that even though it’s software, it’s more drug like in that it’s directly targeting and activating the dysfunctional physiology in the body. You can measure that and by virtue of that, you’re having a really unique effect.

Eddie Martucci: The second big difference is we are using algorithms that have not been ever reported on before. So we take much more of a drug lens where we actually do protect we patent our technology. So we call this whole class “physiologically activating digital therapeutics.” Some people have referred to them as mechanistic digital therapeutics or disease modifying. There’s different phrases, but this idea of unique algorithms that you actually can protect with patents and copyrights, which we do. So we have about 50 issued patents for the technology that underlies EndeavorRx and another 100 that are filed on our various technologies. And you can demonstrate this has a real, unique physiological effect. I think what it enables, at least for these types of products is a feeling from the health care world that this is much more what I’m used to seeing in my traditional medicine where it’s unique. I can’t just go get this anywhere because I trust that this one product is the only one that has this unique technology. And by the way, it’s been proven to work. And I trust that they’re a stable company that’s going to be around for a while. Those things are really important to our model.

Harry Glorikian: Well, it’s a good thing that I’ve been explaining it to people the right way. So at least now that we’ve talked, you know, my explanation is aligning correctly. So I’m happy about what I’m reading is correct. Let’s take a step back. So, there’s a lot of kids with ADHD who have no problems concentrating on something for hours if they’re really interested in it. But it strikes me the key feature of the of the product is not just keeping kids engaged. It’s supposed to build or improve those skills. Is that the key thing that makes the game special or unusual or different from any other pastime, say, building LEGO spaceships?

Eddie Martucci: Yes, absolutely. So the engagement is critical, but the differentiator is the challenging and improving of that core cognitive functioning. And you don’t get that just by engaging in something. And actually, the vast majority of entertainment products you engage with will allow you to either passively engage, meaning you could watch YouTube videos for hours and hours, but you’re not actually challenging your brain or actively engage, but in a way that you don’t really have to challenge what you don’t do well. So in most video games, you can choose what most of us do in life, choose the path of least resistance, because we like certain ways of using a product. Our product is unique in that this this patented algorithm forces you—it’s essentially measuring second by second where you’re weak and processing the various streams of information and it is forcing you to work on those areas where you are weakest. But it’s doing it naturalistically. It feels like you’re using a treatment, but it’s really that level of focus on, for lack of a better word, it’s really that level of focus of delivery of that algorithm that’s actually going to stress you where it, for lack of a better word, hurts the most. That is the differentiator. The other big differentiator is, is the personalized algorithms that that we built in. And this is where, frankly, technology and data rich medicine has never gone before. But within seconds of using the experience, this product is tailoring to each individual user. And this is true whether we’re talking about kids with ADHD or some of our trials and products and adults with depression or MS, these products can actually tailor to your functional level and then move you along from there. So those two those two bits of how the algorithm works are critically important. The engagement is really the delivery vehicle to make sure you’re getting that level of medicine.

Harry Glorikian: Yeah, definitely, if this was available to people in a larger age range, there are people that I definitely need to recommend this to when well then that becomes available.

Eddie Martucci: But well, that’s the interesting thing about cognitive dysfunction, right? The way I talk about it sometimes is cognitive functioning and or problems with cognitive functioning go across disease, right? They’re in many ways disease agnostic. Almost anything that touches the brain results in some level of cognitive dysfunction or at least some proportion of patients that have longer term cognitive dysfunction. But it also goes above and below disease, meaning subclinical. So there are people that are not diagnosed with issues that, you know, that probability-wise there’s 20 or 30 percent that are significantly below the mean they’re struggling with these things. So this is a this is a basic human function that rears its head in a really nasty way in many diseases, but is actually relatable to all of us.

Harry Glorikian: Yeah. So. I mean, there’s a lot of challenges when you’re trying to design something like this. A ten year old will not spend much time playing a mobile game unless it’s it’s just as compelling as, you know, anything that they could download as a mobile app. So. How did you guys, what steps did you guys take? You know, it’s almost like game design and, you know, therapeutic outcome, you know, together in one package. And so how did you guys, what steps did you guys take to make sure this thing was fun?

Eddie Martucci: Correct. Yeah. And it does depend on the population. Right. So we have products, obviously a marketed product in for children with ADHD, but we’re developing products and have trials and data and adults of various ages. The I think you’re right. If you focus on children, there’s a there’s an engagement bar that is not easy. Right. Kids are highly discerning. They know a good game and a bad game. And what we like to say is we have no delusions that we’re going to come out with the next blockbuster entertainment game. That is not how we built the company. However, we do want to have a game that looks and feels like the type of games that you actually like to play. So it has to be worlds better than edutainment, as people call it, educational software, because kids know. And so the way we did that is this is one thing that makes Akili very unique. Instead of outsourcing or kind of outsourcing game development or adding game development at the end of our development cycle, we actually have built the company to have cognitive science, clinical science, and game development fully integrated from the earliest days. And data science, for what it’s worth, is really a kind of foundational thread for all of those. And it’s hard. It’s really hard. I mean, developing a product that has both these things, the strong science and the engagement, is really hard, but it’s also really hard for people from all these different industries to, you know, be speaking the same language and work together because the development processes are different, the language you use is different. Your mindset of how you think about developing is different. And so for us, what I always talk about is it’s literally daily attention. I’m unwilling to sacrifice or give up on it. We have to do both. Well, I think where we are today with EndeavorRx as our first product out of the platform, it’s a really good product. It was built to show clinical efficacy and engage people to a minimal degree. It does that. Some kids love it. They will play for months at a time, you know, five days a week for four months. But yeah, there’s a lot of people that kind of get through it and then plenty of kids that say, I really don’t want to use this. So we’ve built features around the edges, things like an app for parents to allow them to track and monitor and incentivize their children. And we try to educate our users on why you’re doing this. And so it’s got to be a mix of the engagement itself, but also a little bit of inherent motivation that, hey, your doctor’s in the loop, this is your medicine. It’s important to put the work in and accomplish it.

[musical interlude]

Harry Glorikian: Let’s pause the conversation for a minute to talk about one small but important thing you can do, to help keep the podcast going. And that’s leave a rating and a review for the show on Apple Podcasts.

All you have to do is open the Apple Podcasts app on your smartphone, search for The Harry Glorikian Show, and scroll down to the Ratings & Reviews section. Tap the stars to rate the show, and then tap the link that says Write a Review to leave your comments.

It’ll only take a minute, but you’ll be doing a lot to help other listeners discover the show.

And one more thing. If you like the interviews we do here on the show I know you’ll like my new book, The Future YouHow Artificial Intelligence Can Help You Get Healthier, Stress Less, and Live Longer.

It’s a friendly and accessible tour of all the ways today’s information technologies are helping us diagnose diseases faster, treat them more precisely, and create personalized diet and exercise programs to prevent them in the first place.

The book is now available in print and ebook formats. Just go to Amazon or Barnes & Noble and search for The Future You by Harry Glorikian.

And now, back to the show.

[musical interlude]

Harry Glorikian: What makes you optimistic? Because I’ve been, you know, enamored with this space for a while now and trying to watch like where it’s going to grow and what’s going to get in its way. And so what makes you optimistic about digital therapeutics, either as a venture scale business or a public company. Because I know you guys are thinking about that. Tell me what you’re thinking.

Eddie Martucci: Yeah, a couple of things that make me very optimistic. I think the foundational groundwork is now done and we’ve shown it can be done. So we know that these products now can be developed, they can be protected, they can be brought through clinical trials and actually help patients. That’s the most important thing. They can undeniably with strong clinical data, help patients and they can be brought through the FDA and now being prescribed by docs. So these prescription digital therapeutics, there’s only a couple of them on the market. But literally at this point there’s been now thousands of docs, not merely tens or hundreds, but we’re talking now about thousands of docs who have prescribed prescription digital therapeutics to patients, where a couple of years ago that would have been essentially zero. So the foundations are there more. Every month that goes on, it becomes a a self-fulfilling cycle where doctors and patients hear about it, they’re aware of it. They know someone who’s tried it. And it’s becoming a little bit common nature to think, wait, isn’t there something digital that I’ve heard about for this? I think that will flip in the coming years to I expect to have a digital treatment or I expect to be told the digital option for my doc. So that makes me that makes me optimistic is that the groundwork is there. We know it can be done.

Eddie Martucci: The second thing is, frankly, society is demanding better medicine in many different ways. They’re demanding, and mainly I’m talking about patients in many respects, they’re demanding more accessible medicine. They’re obviously…we all got the efficiency bug of telemedicine during COVID. And while I’ve seen the data that that has significantly receded, I don’t think the concept of online or digital in medicine has receded from anyone’s mind. I think we all know that it’s far more efficient and we should expect to see more products that are digital in nature, whether that’s scheduling with a doc or taking a treatment. And so I think there’s this kind of wave in society that is that is pushing people to recognize that we should be open to these types of products. The other thing is, whereas docs and patients years ago when we did market research, there was a level of skepticism that was pretty healthy. I now see a level of openness where if there’s good data and there’s especially in our case, things like FDA approval and strong clinical data, there’s a better chance than not that both patients and doctors are going to be not only acceptable or accepting, but they’re going to want to at least try something like this. So all the groundwork is there. We’ve just got to keep keep plugging away because it’s new.

Harry Glorikian: I talk about the whole digital therapeutic space in my book. And I always tell people look, if a product like this works for you, you’re not going to have a side effect profile the way you have with some of the small molecule drugs that I’ve seen. It’s trial and error with those things. And sometimes things don’t go as well as you want them to and you end up with a very angry child if the drug doesn’t do what it’s supposed to do.

Eddie Martucci: It’s egregious. It’s egregious. I mean, medicines, pharmacological medicines for neurological conditions are critically important. Don’t get me wrong, I think they’re critically important. And EndeavorRx is not meant to be an alternative to medication, especially if it’s working well for for a child. But the problem is, there are many components of these conditions that are just not well addressed. And so you’re left as a clinician to try to use these blunt instruments, these molecules which weren’t delivered for these problems or rather weren’t designed for these problems. You’re trying to use them, but you’re fighting the side effect profile as much as you’re fighting the efficacy the whole time. And so you’re right. Trial and error is the right phrase. Like the fact that we’re still doing trial and error in CNS conditions all these years later is crazy. And there’s a better way because we now can have these more targeted products that are part of the patient’s toolbox.

Harry Glorikian: Yeah, and we need more of them, so. Yeah, great. But let’s talk about the business model, right? I mean, this is, you know, feels like fresh territory, right? And if I think about mobile games generally don’t make money unless you sell millions of copies. Right. So you have you must have a different business model in mind from the beginning. I suspect this business model revolved around, you know, selling Akili games as a prescription based therapeutic at a cost that would be more typical for a drug than a mobile game.

Eddie Martucci: Right. Right. So the concept here is we want the products to get to the patients that really need them and we want to involve the doctor in the loop and we want to have products that are proven. And so all of that to me says a core medicine model, meaning prescription treatment, as you said, covered ideally by insurance largely, but with a little bit of out-of-pocket burden from the patient. You’re right, the general cost is a little bit more in line with pharmacology, although the good news in mental health and behavioral health is that’s that’s relatively inexpensive. We’re not talking about multi-thousand-dollar therapies here. We’re talking about something that is in the low hundreds per month. And for the patient, really more like $30 to $50 a month. So these are the cost structures that we think are tenable and have been working well in behavioral medicine. And that’s really where we’re starting. But we’re in the early days. I think one of the beauties of digital is we don’t have to just stay there, meaning that is the core of the model, a prescription that scales and is paid for by both insurance and patient.

Eddie Martucci: But I think there’s a lot of potential to evolve and iterate the model that has more consumer elements to it. For instance, like your best technology products, we can adapt the product itself to grow with you. Like your best technology products. We can serve, you know, services and help on the side beyond or in between your use of the actual treatment. So there’s a level of connectivity with our end user and consumer that is that actually looks a lot more like best in class consumer software where you can have a long term relationship with a patient. Now, we have not pulled any of those levers yet, but I think what we’re most excited about is the bringing both of those models to bear. A medical model, but that has some aspects to it that can actually grow and extend more like software. I actually think that’s where the field will go. But it is early days. We’ll have to see how this we’ll have to see how this shakes out.

Harry Glorikian: Well, that’s why I always I always tell people, like, you know, once you digitize something like you get to have a broader imagination about what is possible in that realm as opposed to, you know, sticking to exactly what we did before.

Eddie Martucci: Exactly.

Harry Glorikian: But taking a step back here, no one has ever marketed a prescription based video game or won marketing approval from the FDA for such a product. Right. So how did you frame yourself? You walk in there and you say, “Hey, here, play this. And you’re going to like it.” What were the hurdles? What did you have to overcome to get regulatory approval for this? What was it like dealing with the FDA?

Harry Glorikian: No, it’s a great question. Yeah, the FDA process is fascinating. We know it is rigorous, it’s long, it’s mostly collaborative. Right. The FDA wants to learn and help. But I think, number one, most importantly, there’s unfortunately a myth out there today that digital therapeutics are actually medical devices generally don’t have to go through efficacy analysis by the FDA. So I see this myth all the time. People say, well, you know, on the medical device side, they only look at safety. And so, unfortunately, with broad brushes, people have painted digital therapeutics as part of that. They’ve said, well, digital therapeutics may or may not have evidence, but the FDA looks at safety. I can unequivocally tell you that could not be farther from the truth. I would say 95 percent of our interactions with the FDA, which took the better part of two years because our product was so novel, you can imagine we were not only innovating the delivery mechanism, it’s a video game. We were innovating the target, which is cognitive functioning, which there are no products labeled for cognitive functioning. And we were trying to look at what are the endpoints that, you know, that read on cognitive functioning. All of this is new, but not 95 percent of the questions we had, and that’s—please don’t quote me on the specifics, this is not a deposition—but in that range, were about efficacy. And we went through every little bit of our efficacy data so that the FDA could understand it, so that they could audit it.

Eddie Martucci: We even, midway through our regulatory process, brought on a fifth study. So we have five studies in our FDA label package. So we brought on the most recent study to show to address some questions FDA had around efficacy in the longer run or efficacy along with medication. So this was a very rigorous process. I always tell people the good news about this is you can trust it when it comes out because this is something that looks and feels a lot like the drug process, right? There’s a lot of scrutiny put on the trials and the legitimacy of the trials. So so it looked a lot like that. It’s highly iterative. From a business side, the one tough part with FDA is when you’re when you have a new classification for a product, so a 510K de novo, so they’re creating a classification, there is no hard timeline on the review. And so when you’re a startup and you’re building a business, you kind of just keep iterating until you get to a label or not, right? And luckily in our case, we did. But yeah, I mean, as a startup, you’re going through a nearly two-year approval. It’s stressful. It’s stressful, but it’s good for the industry, I believe, because it’s really forcing a high bar of science.

Harry Glorikian: Well, no. And I mean, that’s what you want. You don’t want a low bar and then things go wrong, like you want it to be held to a higher standard. And usually when the FDA is taking on something new, they’ve also got to take the time to catch up to where you are. Right. They can’t just walk in the room and be ready for this. So you’re sort of paving the path for everybody that’s coming behind you, which is a I guess there’s a good part of that and a bad part of that.

Eddie Martucci: Yes. Yes.

Harry Glorikian: So there’s a lot of stakeholders and gatekeepers in this space that we’re talking about, right. Patients, parents, physicians, payers. I mean, each one of them needs to be persuaded that digital therapy or digital therapeutics are, you know, beneficial and worth prescribing or worth paying for. So, anything special you’re doing to sort of win them all over?

Eddie Martucci: Well, we’re doing the work to put time and attention towards it. So you’re right. Just because it’s digital does not mean people will use it or understand it. So you’ve got to sit with patients and educate. Just because docs have a new tool doesn’t mean they’ll trust it. So you’ve got to spend time to make sure they understand the data and more importantly, understand where we’re trying to play in the treatment paradigm. Right. Because, again, we’re not … the easy answer for a digital is, “Oh, this is supposed to be a digital equivalent of a drug.” No. It’s more nuanced than that. This is supposed to help in a very specific way. And insurers are probably the biggest barrier because it’s so new for them. Right. This is this is very new. They don’t really, they’re not really built to be able to adjudicate digital products. Right. And unfortunately, we’ve got some of these types of myths floating around, like the FDA medical device myth, which understandably makes insurers uncomfortable. Right. If they if that’s what they’ve heard, they say, well, how in the world am I supposed to adjudicate efficacy if the FDA doesn’t? I guess I’ll look at this with all the other hundreds of wellness apps out there.

Eddie Martucci: So it’s education time. Honestly, it’s education time to unravel these myths, to really sit and make sure these stakeholders understand the data and the utility of the product. In terms of special things, one of the one of the nice things about growing a company, especially with digital company in this day and age, is you can test and iterate really quickly on all of these fronts. And so when we test you’ve got to have the meetings and you’ve got to fit into their review cycles. But for patients and docs, you know, we, we take a very clear test and learn approach. We are releasing certain types of educational content or certain types of marketing messages in pilot phase. Right now we see what works, we see what doesn’t. We adapt. We do the same thing with the distribution infrastructure, frankly. Like how in the world do you get a video game therapeutic from your doctor? We built the infrastructure. We tested, we changed, we scrapped half of it and started again. So that is the beauty of living in a digital world. We can we can do that type of testing and learning.

Harry Glorikian: And good old AB testing on what works and what doesn’t.

Eddie Martucci: Totally.

Harry Glorikian: All right, let’s step out of ADHD for a minute. You’ve been talking about other neurophysiological sort of conditions. And I think the website, if I’m not mistaken, mentions depression, cognitive dysfunction, multiple sclerosis, autism spectrum disorder, and a few other future treatments is. Is there something about the EndeavorRx platform or the proprietary adaptive algorithm that gives you the ability to sort of generalize? And I think you mentioned that earlier, but sort of to dig into that a little bit.

Eddie Martucci: Yeah. So it really starts with what technology are looking for. And so we don’t source technologies that are meant for any one condition. That is more common in the behavioral therapy space where there’s behavioral therapy for disease X because it’s a tried and true technique specific to the disease. The way we work is looking for technologies that actually activate specific brain regions and have data that they do that well. And so the interesting thing that we found about cognitive functioning, and we knew a little bit about this, but you know, I don’t like to have revisionist history and say we we knew it all, with cognitive dysfunction and disease, independent of the etiology or the cause of why the brain is having issues, the downstream manifestation actually tends to bucket into very similar issues. And so our theory was, and so far it’s proven true, is if you could bring technologies that are meant for the neurological processing issues, not the disease, not specifically the disease, then any condition that results in similar issues, you should be able to have a functional impact on. Because we’re not we’re not targeting, you know, dopamine reuptake and a dopamine driven disorder. We’re not targeting myelination in am anti-myelinating disorder. We are targeting the end result, which is how well the brain is communicating. So we’ve because we start there, we, we theoretically have the ability to go across disease, and we’ve actually shown it now. So the same technology that has a treatment label for ADHD has been able to power two studies, including a larger randomized controlled study in multiple sclerosis adults, and showed clinically meaningful, large changes in speed of processing and related cognitive functions. That’s the same technology under the ADHD product. ADHD and MS could not be farther from each other in terms of cause, but because the resulting functionally in the same in the same area, that’s then you get that benefit. So that’s our theory and that’s how we’re going to continue to develop products and take a functional and a neural network approach, if you will. And, and ideally, we have a much more efficient product pipeline because of it.

Harry Glorikian: So. In your mind, like what are the biggest unanswered questions, either for EndeavorRx or for the Akili business. Is it more product? Is it more market? I mean, for example, do you worry about whether it’ll work, you know, in the real world, as well as it did in your initial studies, whether doctors will prescribe the game, whether payers will cover it. There’s all these issues. And so I’m just wondering where you think the biggest hurdles lie?

Eddie Martucci: Sure. Yeah, I think I think my number one is not about the product. It’s really systemic to the to the health care system and industry, which is it’s important to me that the insurance industry, the doctors write prescriptions, but more importantly, the insurance industry and broader we could call it the payer industry. Right. Anyone that should be paying for medicine pays for digital therapeutics. Right. I don’t think this should be the only class of medicine where patients bear the entire cost. That makes no sense. So we are not there yet for sure. Right. We’re in such the early days that I think some payers are waiting, but I think we’re starting to see a turn. We’re beyond skepticism, beyond intrigue, probably into early acceptance. And I think the work needs to be done. And frankly, we need we need a couple folks in this industry and by folks, I mean both people, but also organizations to step up as the early pioneers for their patients. I think that’s really important. Now, again, I have empathy for why that part of the industry moves slower. They’re trying to protect patients. There’s obviously cost arguments as well. And there are some of these myths or misconceptions out there about the industry. But I think when education is done right and when payers really engage, we’re going to start to see a broader payer ecosystem adopting this like they would any other medicine. So I think that’s kind of the biggest near-term barrier. And slightly longer term, I think the business model is a question. Which no one likes to hear, no investor likes to hear. And we’re a company that’s going to go public. I don’t mean the business model is a question in that we don’t know if we can make money or build a business. I just mean, what is…so, the foundations we know are there. Doctors will prescribe, patients will pay, payers are starting to pay. It has a benefit in people’s lives. So the foundations are there. The business will grow. What the eventual business model is, is TBD, frankly. What is the top end business model that’s going to allow a company to thrive at scale? I think we have to invest to learn that. And I’d say the same thing about the product. In terms of the product, it’s not whether it will work, it’s not whether it can help patients on the market. We’ve shown all of that. It’s at this point, how well can you develop that product on the market so that it engenders long term compliance so that engenders loyalty and use in the future? And so I think in both those scenarios, I guess the health care system’s got to get there. Which is a secondary priority, more like an opportunism. We don’t want to miss the opportunity to find the best business model or to iterate on the products because we have the ability to do so. I don’t want to miss that opportunity to grow the best business model we possibly can.

Harry Glorikian: So you mentioned going public once or twice, and so I saw that there’s paperwork with the SEC to go through a public filing with a special purpose entity backed by Chamath, whose I think it was Social Capital, through his venture fund. What’s the thinking behind becoming public? Why now?

Eddie Martucci: Yeah. I think I always had a mantra and I didn’t come up with it. This is from advisors to me and mentors: Stay private as long as you possibly can for the business to be able to adapt and iterate and a little bit more of a clean way. But I think that time has come, and the reason I say that is we have a product that is being prescribed by doctors now and we have a pipeline where I’ve already talked about it. We could help potentially up to dozens of different populations who are struggling today. On top of that, the need and urgency around mental health and behavioral health has had a step function change in the last year. Right. We know that President Biden talked about it at the State of the Union. The surgeon general has put out a national state of emergency on youth mental health. So the time is right for a real investment here and the time is right for the company to fill that need. We know all the all the foundations are right. So I’ve always wanted to wait till that moment why we chose this specific entry point and vehicle, which we hope is kind of middle of this year, that Akili becomes a publicly listed company is, I think, the opportunity to not only have capital and the type of flexible capital that the public markets gives you, but in the case of a special purpose acquisition company, the expertise of that acquiring entity, in this case, Chamath Palihapitiya, who’s extremely well known and amazing at building disruptive technologies for different industries that scale to ubiquity using technology and data.

Eddie Martucci: But actually that the SPAC vehicle here is Social Capital Suvreta. Suvreta being a well known biotech hedge fund who specializes in early commercial biotech companies. So rarely do you get to become public with the right amount of capital, but also some new expertise around the table, strategic expertise in a disruptive business. And I think we get both of those with this deal. So we’re still, it’s too early to tell if the whole thing will go through. We’re certainly crossing our fingers and hopefully if people listen to this in the longer future, Akili is already a public company and thriving.

Harry Glorikian: Well, I mean, it’s a good thing I spoke to you now so that we could speak a little bit more freely than when you’re under that public rubric.

Eddie Martucci: But oh, no, I’m already I’m already watching my words. It is important. It’s a level of maturity as a business. Now, we have we’ve grown for about a decade. We grew methodically and slowly. We have over 100 employees now. And, you know, businesses change and mature. And I think it’s the right time for us to do it.

Harry Glorikian: Oh, yeah. I mean, a lot of the companies that I interact with as an investor, I mean, when we’re going to go public, it’s like, “Oh, we got to do this, we’ve got to get that ready. We got to get accounting ready. We got it.” I mean, you’ve got to go through it methodically because being public is is not for the faint of heart for sure. So, well, I wish you the greatest success. I look forward to staying in touch and, you know, keeping up to date on how things are going with the company. And, you know, I hope a ton of people listen to this because it’s easier for them to hear it from you than hear it from me.

Eddie Martucci: Thanks, Harry. This is a lot of fun. And thanks for your focus in innovation and these new areas that are really going to transform patients’ lives. So I’m hoping we’re doing our part there.

Harry Glorikian: Thanks.

Harry Glorikian: That’s it for this week’s episode.

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