#421 Daniel Månsson from Flow Neuroscience: Is Electric Brain Stimulation as Effective as Antidepressants?

0:00Welcome to the Health Tech Podcast. Here we talk about everything healthcare and technology. and I'm your host James Someru. Hey everybody delighted to be joined by Daniel Monson who is Chief Clinical Officer of Flow Neuroscience and if you haven't heard of Flow Neuroscience firstly where have you been but it is a class 2a medical device it's a headset kind of a headset I don't know if that's the right description actually but we can talk about that Daniel but it's the the treatment of unipolar major depressive disorder in adults so it's an alternative to drug therapy and it uses a technology called tdcs which is transcranial direct current stimulation which delivers two milliamps microns milliamps milliamps milliamps um to the left dorsolateral prefrontal cortex which is crucial for emotional regulation so daniel whereabouts are you based where are you speaking to us from you are you still based in sweden i know you've got a global company now so uh yeah where do you like to base yourself so i base myself and my co-founder is also here in malm in sweden so that's um next to copenhagen which is uh more people know about that and the capital denmark but it's just across the bridge here so i'm very close to copenhagen but in sweden very nice so i imagine that's where you grew up right no it isn't actually it's like uh 20 miles uh swedish miles south from uh so malmese south from veck which is where i grow up oh wow so what takes someone from a place like that in sweden to owning a global neuroscience company or or neurotech company that's now making all this impact where does the journey start for you what made you interested in the sciences or getting involved in this specifically where does this journey start for you yeah it's uh as you could imagine from many other interviews with entrepreneurs.

2:20It's a kind of up and down kind of journey, of course. It started in a quite small town, growing up with two parents and two siblings, which are older than mine, than me. And quite entrepreneurial home. My father ran a business, always worked for himself. but in the construction businesses, a little bit of IT and so on. But I was always around that kind of environment. And the same is true for my brother and my sister, who both have been CEOs for smaller companies, which is a little bit strange, actually, because when you meet them, you don't get that vibe at all. But not a very academic home, but still decided very early on that I wanted to study psychology.

3:17Basically, when I was 14, 15, something like that, and decided that I wanted to kind of explore what I felt was the real emotions of people. So I saw people acting in a certain way and saying something different very early on. So I wanted to explore what is the real driver of action in people. So that's why I started studying at the very beginning Freud, started reading Freud and didn't really understand it, of course, but I was very fascinated by both Freud and Jung and all that old guard. So do you believe in free will? I don't. Not on a philosophical level, no. I'm a big reader of this Stanford primatologist I believe he is, who wrote a recent book about free will and I'm a big believer in what he says about free will, that it's a deterministic process and so on with complexities around quantum theory and so on, but still at the very highest level I believe it's deterministic.

4:28Interesting. So what next? I was also very interested in in computer science. So I started building computers and doing some programming and so on and hacking was a big interest of mine, white hat mostly. So when I was 19, I took a bachelor in computer science at university. So very interested in that, but discovered quite early on that this was not my kind of passion. So then took a brief stint into the construction business together with my father. We started a company with a new type of construction method, you could say, where you build in solid wood. But then really understood that, okay, it's psychology that I want to do.

5:24So fast forward, took a psychology degree as a clinical psychologist, practiced for about two years worked in Norway in a hospital there a psychiatric hospital and for different reasons I came in contact with Eric my co-founder who was then leaving startup you could say very well-funded startup in Silicon Valley and came home to Sweden and we decided to start this company so that's like a very compressed version obviously of my of my life up until 30 but that's the way it started when you mentioned hacking you said white hat what does that mean so it's a it's a term that you use in in that space where you can have you can be a black hat i mean taking down like government systems oh right okay hacking like proper hacking uh illegal stuff and then you can be a gray hat which is kind of in the middle and the white side is more like you you learn systems and you understand like how you do i don't know back in the days it was like buffer overflows you could do like writing over memory and stuff like that so you can get into other processes of the system so it's just your way of saying i do nothing illegal that was just your way of saying that exactly nice what's the difference in the type of people that do uh black versus gray versus white psychologically speaking I think it's the same difference as you have with any type of criminal person versus someone who's just interested in security.

6:54I mean, you can do lockpicking for fun and you can do lockpicking because you want to steal other people's stuff. And I guess if you want to do a deeper psychological kind of persona of them, I would say that it's a little bit understanding consequences. and morality and having the feeling of morality. So we're going to psychopathology. A psychopath, for example, could go over those lines, but another person would feel bad if he did that. When you did the degree in computer science, coming from psychology, did you did you have an appreciation for or what what did you learn about perhaps the way we're building AI and computers and how that relates to psychology because one thing I had a conversation with someone recently that that said in in the pursuit of building AI we're sort of learning more about how our own brains work because we're having to put this artificial system in place that is almost mimicking how we think and you know in the universe we can't a knife can't cut itself fire can't burn itself and trying to create ai to understand ourselves is perhaps a bit of a fool's errand but did you find a link between the two did you find an interest between the two of computer science and psychology yes definitely i started the other way around so i I studied, I mean, I read Freud and stuff like that in the beginning, but not in a formal university kind of way.

8:38Oh, I see. Until after I did the computer science stuff. But I would say that definitely I remember a session that we did on psychoanalysis. And we sat together in a room during my education as a psychologist. And we sat together in a room and people or the teacher asked us why we choose this field. And people had all sorts of reasons. But I stood out a little bit because I said, I really want to understand systems, which wasn't really what they expected. And that came directly from the computer science stuff. I wanted to understand. I studied specifically network, computer networks and the Cisco education.

9:19So I'm a Cisco certified network professional. But it's way back, right? So it's basically an understanding of systems, how they interact together and how information is flowing and stuff like that. That then was quite helpful, actually, when I tried to approach the understanding of a part of psychology, at least the more neuro parts of neurology and even on the computational side that we can come to later. but Eric and I met at the computational neuroscience department at the KTH which is a technical school so everything like ties together obviously there's a big part of psychology that has much more to do with with having rapport with the person and understanding emotions and so on that's a little bit less connected to this system but to answer your question I think they're married very nicely together so where did your thought process start to come in that a different type of therapy could be used for depression where did the idea for flow neuroscience start so i would say that it starts actually in an incubator during my psychology studies and there during the summer I had a project, it was a software development project that had to do with testing, intelligence testing.

10:54During that time, I saw a product ad for a type of equipment that delivered this type of current that we're working with right now. And I was just very intrigued and I thought, okay, this is, what is this? So I started researching it and then fast forward, I did my master thesis on this technology. So we use this technology in order to enhance attentiveness in people with difficulty, yeah, had difficulty with attention. So the whole spectrum, mild to up to ADHD as a diagnosis. So we got some interesting results there. And based on that, I started traveling the world and went to the different scientific conferences.

11:51I remember being in New York a couple of weeks and doing kind of a training workshops and so on in this technology. and then went to Göttingen, which is basically the starting grounds for this technology in Germany, and many other different places. And then understood very clearly that this is a very emerging, very interesting field. It's growing quickly. The science that is coming out of it is very thorough, but it hasn't really been published yet. So it was like in the very, very beginning. The trials were done, but they hadn't published yet. And came into contact with some professors there and up and coming researchers that were really clever people.

12:42And I thought, OK, this is very interesting. So this is kind of how it started in my mind that this could become something that could be not a rival, but another tool in the toolbox for treating this disease on scale. And is that because you had a hypothesis around an area of hypoactivity that was connected to depression? Was that clear science at the time that you thought, okay, there's a technology here that can stimulate a region. There's a region that needs stimulating. Therefore, we could do that with depression. Is that what you linked together? I wouldn't say it was that sophisticated in the very beginning.

13:31I, of course, knew the theory around what the technology was supposed to do, that you increase the activity in the form of firing neurons. And also knew about the long-term effects in the form of LTP and LTD in other areas of the brain. So we can get into that also, but long-term potentiation and long-term depression of activity.

14:02but I think at that point it was more like the safety profile of this is really really good even then it was clear that if you look at the antidepressants you have so many people with these like sexual problems which is a really really difficult thing for many people and weight gain and many other different things that people have just come to accept. And, of course, if you go out of depression, it might mean, I mean, that's a great risk-benefit kind of analysis that you're doing and an outcome. But it doesn't have to be like that, was my thinking. And then, of course, the effect wasn't super clear what the efficacy of this was but that it was possibly on par with an antidepressant which we also can discuss what that's what those results actually mean but um but that was my thinking in the very beginning it wasn't so much theoretical like linking this to that it was more like a very practical approach to it sure and that practicality starts seemingly with the fact that you are able to stimulate the brain with a small amount of current and you could increase attention in people and looking at people with attention deficit and attention deficit hyperactivity disorder adhd that must have been a very as you say it was very early but very very interesting for someone that's clear from an entrepreneurial family entrepreneurial minded and is thinking about where this could be used in other things that you're interested in like depression but that i'm thinking now again from a from a medic's point of view that we're trained to be cynical about these types of things right so to to hit to hear about a micro current through a headset and now you've genuinely changed an expression of somebody you've changed something in the brain so much that something that we have pathologized i.e adhd can now actually be you know somewhat solved that's a that's a really i mean quite powerful link right to see that at the first for the first time were you cynical at all to begin with and what what what did you what did you okay so what did you need to do and i guess i'm speaking from an audience challenge here point of view like there's there's gonna be many people listening that will google flow neuroscience they'll see the headset and it's like okay cool this this is this is going to do something to depression right so you you've overcome some sort of cynicism in that part when you were looking at it for adhd so what what did can you talk me through like what you went through in your own mind in that period and how you came around to appreciating the the the efficacy of it yeah you're ready for a long one here so i think this is important though that yeah i think this is a really important part I have to stress something here.

17:12I started this company with Eric, who's a computational neuroscientist, very theoretical, does not have a clinical background, very thorough thinker, logical person. If it wasn't for Eric, we would have never started his company. We would have never come this far. Obviously, he's been the most important decision, if I may say so, that I made during this journey. He's been great. We are both super skeptical people, especially when it comes to scientific claims. And we have had so many discussions. So to answer your question, in the very beginning, the only reason why we started a company is because maybe because I come from this entrepreneurial family, I could see the possibilities.

18:07So I could see the possibilities that, okay, it kind of makes sense. It kind of like the science is reasonably good to take a chance on. the safety looks good and and you also have to understand the history of like the ect and so on so that kind of safe safety discussion goes into uh what we believed uh could be a very safe method to be just just for listeners here daniel i i think ect ect is something that that's just worth like spending a minute on here ect for those people that don't know if i've got this right from my medical training is electroconvulsive therapy which we had to see as medical students we had to get it signed off and it's a it's a treatment i believe for almost treatment resistant depression where yeah you are yes where you're essentially i mean you're essentially electrocuting a patient under anesthesia like you're you're delivering a lot of electricity to the point where they convulse where they they fit they they fit like a similar to an epileptic seizure they have a seizure under anesthetic um and then you wake them up and explanations again pulling from from a long time ago this was now but um of resetting uh certain areas of the brain and and that kind of thing i'm going to butcher that you'll know much better than me um but worth pointing out that for treatment result or drug treatment resistant therapy this is where you could you could go to this and it's not it does not seem a pleasant treatment to be part of whilst it might work um in some cases like it it feels very i don't know like it feels like victorian or very sort of odd odd that we we still do this it's almost in the sort of lobotomizing category that it seems a bit barbaric for what what we should be able to do with science and technology now so i think anything that contributes to us perhaps not needing such a therapy certainly for me feels like progress yeah yeah and it feels like that i just have to add that it's the most effective treatment that we have in the disorders category the effect sizes are crazy Okay, so it's a very, very effective treatment.

20:36Most people don't know about this, but if you look at Sweden, actually have one of the best quality registers from ECT treatments in the world. And the effect sizes for this treatment compared to a placebo, for example, is very, very high. It comes with side effects, and that is a long discussion in itself. but it's a, and I should also say that this is 800 milliamps. And as you said, the purpose is to have this electroconvulsive effect, right? And ours is 2.0 milliamps. So it's not even on the same scale. But ECT is something that you can use when you talk about safety, because we have these long-term kind of registers when it comes to safety of delivering this amount of current.

21:28And then you go down 400 times and then you're at our level. So that's very useful. But so coming back to that kind of approach, I would say that the safety profile, very, very good. And the efficacy is still uh at that point in time uh something that we're discussing but um but yeah very promising technology back then what helped you overcome your cynicism for it was it seeing the results of what you were seeing in increase of attention or was it partaking in research yourself and seeing it that way how did you overcome that cynicism yeah and i i told you in the beginning of this story that you're ready for a long one because I would say that and I remember it quite clear it was a discussion that we had during a dinner and it was maybe two years ago or something like that where we finally decided me and Eric but now we are 100 % convinced that this is an effective treatment that's two years ago in a 10-year journey with the company not that we would release anything to patients that we weren't convinced has a probable effect and that where the safety is 100 % controlled it was never like that but we had a very high standard and a very high rigor when we talked to each other and with other people in the company of course about when we finally believe that this is actually and it's connected to the trials so it's connected to the pivotal trial that we got published now in October of 2024 in nature medicine but obviously we know the results a lot earlier than that and that was a very very rigorous study and we were it was a research-led study it was done at the University of East London and one site in the United States.

23:38And they wrote the protocol and did all the analysis and everything. It was a fully disconnected study like that, but we funded it. So we obviously had input on the protocol and we knew it was a very, very rigorous study. So at that point, to answer your question, then we knew this is the real thing. So let's talk about that then. let's talk about the way that you administer the two milliamps and the the that science of the headset what part of the brain is it working on exactly how is it working what is it doing and then we can talk about some of those numbers in the study because again i think that's quite important i think you told me before this interview started that i should be clear when when I'm not certain about something.

24:36We like being authentic on this. Yes, I fully agree with that. So I should say that we have a bunch of good hypotheses about how it works. The main one being that you apply a current, in this case, to the, as you said, left dorsolateral prefrontal cortex. And what it does is that the hypothesis pushes the neuron into a position where it's easier for it to fire. So you have this potential between the inner parts and the outer parts of the neuron. And if you reach a certain threshold, it fires. And it fires because you get inputs through the dendrites down to the core of the neuron, the zoma. and we apply the current so that this threshold, not the threshold changes, but the potential between it changes.

25:34So it's easy for it to fire, easily put. And that's the hypothesis. But then there are other hypotheses that have to do with how does it actually, is it really the current just applied to the soma or does it have to do something with the vascular activity? so that you increase the blood flow instead and that that increases it. So we're not 100 % certain about it, but we know for a fact that if you apply current like this, you can see the activity in this area go up. You can see it with EEG. You can see it with blood flow in the form of fMRI studies. You can see it in modeling. So you can model a brain in the computer, which is basically what we did at KTH, me and Eric and you can apply the current from a computational kind of perspective and then you can see that the activity goes up and you can also do what they did in the very beginning which is that they used TMS first and if you point to TMS coil, maybe for the listeners TMS is transcranial magnetic stimulation so it's a little bit more powerful in the sense that you can get the neurons to fire without any type of other input which is also used for treating treatment-resistant depression and if you apply TMS on the motor cortex you can clearly see that if you hit the right spot you can get the finger to twitch right and so you can prove that you can actually get to that area as you can see it in the finger It twitches.

27:20But in order to show that TDCS works, they first applied TDCS to this area and then applied TMS and you get a stronger twitch. So you have primed the kind of area. So you can prove in that sense that it actually reaches the brain. Now, that is for the motor cortex. And there's been discussions about does that actually work on all areas of the brain and so on. But we'll leave that for now. But there are many different ways of showing that it reaches the brain and so on. Then you can start talking about, like, how does that become a behavioral outcome? And as I said before, that's a big leap. And the only thing that I can think of, the only way that I can think of in order to prove that that's actually happening is to do a rigorous placebo-controlled, double-blinded or triple-blinded study on the population that you want to measure it for.

28:26Properly powered, multi-center, great clinicians doing it. and have scrutiny in the form of a good publication that publishes it. And if you show statistical and clinically significant result between the groups, then you have effects. And I'll read this out for you because then it seems slightly less partial. I've read the study. The trial was 10 weeks. it was i believe the biggest um of of its kind it was us and uk patients but 57.5 percent of patients in the treatment group of course went into remission so the so they were in remission which means that they no longer had depression clinically.

29:2764 % had an improvement in symptoms of at least 50%. And patients who took the course of treatment were twice as likely to see their depression go into remission than those in the control group who had the headset on but it remained switched off and of course when we talk about impact factor in the journal that published it there's not much better if any than nature medicine so to your point this works according to this study which as you say placebo controlled randomized clinical trial i also want to just touch on the the mechanisms that you talked about and the fact that we don't know it's okay that we don't know first of all and i think this is part of being of course you know it is part of being in a frontier of medicine if you're at a frontier of medicine you are breaking new ground you are learning new things you don't know and that is okay the point is you've checked the safety of it and then you've conducted research to see that at this kind of level does it work i think that's interesting now being at a frontier of medicine you also have to be open-minded and i think this is one thing that's kind of at odds i think with being a clinician sometimes that we're so fearful of things we don't understand sometimes because ultimately we care about patient safety yes we care and we and we care about not wasting resource on things that might not work or you know there's always the placebo effect conversation and things like that but again i remind people we still don't really know how anesthetic drugs work so i think anything that involves the brain the brain is such a a poorly understood beacon of consciousness whatever on earth the brain is the thing that connect us to everything else and gives us an experience and gives us consciousness and and you know controls everything in about it's unbelievable how little we understand of actually what what what the brain is and what the brain does that i think to be at a point where you're having to come up with hypotheses and test them all i think that shows is that you're at a frontier of medicine i don't i don't genuinely believe that that gives anyone the right to kind of question it in the way that will it will often get questioned by people that don't necessarily understand it so i think it's fascinating for that reason which is why i've followed flow neuroscience quite a while but the other thing i wanted to ask you about next is it's it's not just for me to say that and it's not just for us to say like okay we had a study it was great it then becomes okay now what impact can be made with this what happens in in real world because obviously you know real word evidence and things being slightly different to yes to trial settings um but i will add i looked at your website and you have um five nhs services using float so can you tell me a little bit about that can you tell me how that came about how they are using it for um their populations is it first line is it is it within the clinical pathway somewhere how and and and how did they become confident was it on the back of this was on the back of this trial it's a long uh long journey there also um we decided very early on in in the company's beginning that we were going to go to the UK first.

33:22We had bitched Sweden because we found a lot of resistance here that we didn't really find in the UK, so that we were very happy about that. We started, I would say, the journey with the NHS about three years ago, something like that and it started very um it started actually with a couple of people that were um very interested in in the technology and wanted to drive this project within the system interesting so sort of champions from within the nhf champions definitely um we have a lot to thank them for um and uh they started out with suggesting smaller pilots where we provided the equipment, but they set up the study and provided the patients and so on.

34:14They did the actual treatment and education and so on. So started out small, did some very early publications, not on the nature medicine kind of scale in rigorousness, but more like feasibility trials, see if we can get clinicians to use it, what kind of impact it has in the system and so on. I discovered quite early on that the results were, as we expected from a real world, it was a good result. What we didn't expect was that when we then moved on to these crisis teams with really severely depressed patients with chronic depression, like depression for 15, 20 years, and had problems with suicide thoughts and even behavior.

35:08We got some really great results in these teams also. And then the confidence grew within the NHS and one trust spread to another trust and so on because they heard about the results and so on. But it takes a long time. It takes a long time. Then the budget question is another thing. So I think we have, I think it's seven actually, seven trusts that are using it, but on different levels. So we are reimbursed in one, I believe, or maybe two. But the one is a very important one, is the practitioner health trust. So it's basically for the clinicians within the NHS that want to be treated somewhere else because of confidentiality and things and so on.

35:58They can get treated in this trust, we understand it, and then we're offering that to the clinicians. So, very happy about that. It will take a long time because of everything that's going on within the NHS and so on. But we are a little bit surprised, actually, on how, in that context, how quick it actually goes with spreading the word. so we're very happy about the collaboration and try to nourish it as much as we can and are you aiming to have flow as first line i suppose because of the lack of side effects and and lack of safety issues and things like that it it fits quite well as try this first before anything else and so i'm just wondering where do you see where do you see it in the in the clinical pathway of someone with with depressive symptoms and i suppose as part of that as well what is the relationship between flow and antidepressant drugs if there is one is are they contraindicated are they beneficial with has that been looked at um are you trying to eradicate them completely and the need for them completely like where where what's the relationship like but first of all the pathway and then secondly on on the antidepressant yeah yeah so first about the pathway uh logically uh because of the safety profile and the efficacy that's efficacy that seems to be uh we don't have any head-to-head trials yet but it seems to be on on par when we talk about effect sizes which are interesting in in honestly difficult to compare between trials, of course, but still they look very favorable.

37:48So from a logical point of view, yes, then that it should be a first line of treatment for, let's say, mild to moderate maybe. Then you would need a combination for severe. Then what's tactically possible, because we have to consider these things also, So like where do you spend your energy? What type of evidence is needed for you to become a first line of treatment with guideline changes in different countries and so on and so forth? It's a big machine. That's a different story. But from a logical point of view, I would say that it should, in my opinion, be a first line of treatment together with other things that the patient can choose.

38:32We know treatments are more effective if the patients in this area, when patients can choose to their own preference. So the study, the Nature study had basically two groups. One that got the flow treatment as a monotherapy and one that got it as an adjunctive to an antidepressant. And the antidepressant group had a stable dosage of an antidepressant, stable six weeks before starting the trial. and they didn't have what we call response or they were obviously not in remission. They were still moderately to severely depressed. We added on flow to that group. And what came out of it was that the response rates and remission rates are higher for the group that first has an antidepressant that they're not responding to and that then you add on TDCS to the flow equipment.

39:30The response information rates are higher, like numerically, higher than if you have a monotherapy group. So I think it's like 70 % on the madras, for example, going to response when you add it on to an antidepressant. But the effect size is lower. So if you compare it to the placebo, the difference is smaller if it's used as an adjunctive. so you can so you have to decide that what you think is important um but um so so you could say that it works better for the monotherapy group because the difference between the placebo and the active is bigger but the response rates are higher in the other group so so it what i'm trying to say is that it works very well for both groups but you get a little bit difference in in the comparison to to placebo is there a benefit to using this technology in a in a preventative mindset so what i'm thinking here is obviously we always want to try and move health care to a point of prevention rather than cure and i can appreciate what you're saying in terms of um certainly the size of effect in in mild and moderate once symptoms have taken hold is there a world in which this device is perhaps more widespread than just the purely clinical um as in once symptoms and you've got a you've got a diagnosis or perhaps even for those people that are starting to feel something come on what it's a gray area i suppose as prevention versus cure in terms of depressive symptoms but do you see a world where this device is quite widespread and many people that perhaps don't have a specific diagnosis of depression are using this to prop up their mental health or is this purely effective as a clinical device once people clearly have symptoms yeah it's a very good question and here i have to be a little bit technical because i think that like intuitively i think it could be used as a preventative device but if you're scientifically minded and you're asked about effect will it be effective in that state then what is effective effect is for me is a um rigorous trial that shows now and over time that you will have a certain outcome compared to a comparator or a placebo or or some other treatment and so that's the way to prove it and how do you prove that something is preventative.

42:34Well, the same as you would prove something in the Alzheimer's space, for example, or dementia space. It's a very long-term study, a population study where you follow the people that are doing the treatment but don't have the actual disease. So you would do brain stimulation, but you wouldn't like, right? And then you would have that comparative be a major register of some sort where you can follow other people, healthy people that are not getting the treatment. And then you would prove that maybe five, ten years from now. And it would be an enormous N, a big study with a lot of people, and you will get numbers that the outcome that you are going to present to a payer or NHS or a healthcare system of some sort and you would say well we can prevent this from happening at this scale and please pay for that it's a very very difficult problem but if you just talk if we're just talking here I would say that I can definitely see a situation where you could prevent it from happening let's say that you you get some kind of indication and maybe that indication isn't I feel worse maybe it is a biomarker of some sort.

43:59Interesting. Really interesting. I can't say that much more about this because we're dabbling around in that field. Of course, R &D, you're going to be doing this sort of stuff. Yeah, absolutely. But it's a very interesting area and I see a lot of things happening that looks extremely promising. But that might be a different model. It's maybe the consumer that is paying for it, monitoring, like any other tech product, a watch or something like that. It's really interesting because you're sort of granted the license to do this sort of experimentation and learning because of the safety profile. Because of the safety profile, it is allowing for this, which I think is interesting.

44:52and it again as a speaking of my clinical hat on when something looks too good to be true it often is and so you're sort of you're sort of feeling like where's the where's the catch here but actually until you've until you find it what why not let's like let's explore this and let's do so safely and make sure it is safe and all those things but um so for those people that it does work on can you explain to me the the treatment that flow neuroscience as a company the service that you are giving people so going beyond the science now that okay yes we can stimulate with so how many how many times are you doing this what because i've you know again read read up that there's an activation phase there's a strengthening phase you have behavioral therapy that's adjunct to this as well.

45:42So how have you then taken this technology and built a service that actually delivers the outcome and the impact that you want for patients? Yeah, so I would say that the service right now is a brain stimulation headset, as you said, combined with a behavioral training program, which is written by clinical psychologists in a very thorough way. in order to get this extra kind of effect on your well-being. It's also written from an empowering point of view. We want you to feel that you're in control of this disease. So that's the two components that goes out to the patient. Then we have a back-end, a clinician portal.

46:33So if you want to be connected to a clinician, you can also be that and the clinician can change the simulation schedule. So we have standard, as you said, active phase and more maintenance phase. The clinician can change this. So they can say, we want you to do, because you have more severe depression or because it's more chronic or whatever, we need to increase the amount of stimulation sessions. So that's like three components, but two that faces the patient. so that's the service together with a fantastic support team that we have that will answer any question that you might have about comorbidities about how to use it practically if you have a little bit more of a pain sensation or a little bit more sensation underneath the electrodes then what type of stuff should I use in that case or how should I clean my forehead and so on.

47:34So a lot of support in that sense, but that's the core service. And we have, it's a little bit difficult to do science on this, but roughly around 80%, I would say, maybe even a little bit higher, comes from doing the stimulation. And this is also the only thing that we tested in the trial. So any other type of effects on behavioral therapy comes on top of these results. And then if you do the behavioral therapy program, we can see that people have an additional effect, but it could also, yeah, it has to do with how engaged you are. But the philosophy from the very beginning was you do the stimulation to get this extra energy, to get this executive control, so that you then can make changes in your everyday life.

48:25So that's the, it's still the core thinking around. Where is the flow neuroscience IP within this? What part of it is yours that's unique to you versus what another company might be able to do with this technology? I would say that TDCS, and we should be honest about this, we haven't invented TDCS. It's done by, I mean, if you go back to ECT, they have their slightly different kind of mechanism of action or quite a lot different, but it's still current. And then that progresses. And I would say in the beginning of the 2000s, people started doing real science on transcranial direct current stimulation.

49:15So we don't own that. What we own, though, is the specificities of the headset and a little bit different philosophy around sizing of the pads, safety mechanisms that has to do with how you deliver the current, some design things. And we actually have a quite large patent portfolio. Can't really go into the details of that, but we acquired another company which had a big portfolio. We had a quite big portfolio from the beginning that protects personalization and a bunch of other things. So I would say that the IP is quite interesting because it's an emerging field, but obviously can't go into that much into the details around that but um it's it's um to answer your question the core technology you cannot own but you can own a bunch of different things around it yeah how you do it and also there's the just the organization knowledge of having done this for so long and um yeah somewhat of a first move of advances to just having dealt with patients for so long with this that you guys obviously know what you're doing Yeah, I mean, I think the real note is the science done on this specific headset, but also the regulatory hurdles that you need to jump through in order to get to a safe and effective place.

50:51You guys have scaled quite successfully into multiple geographies now. Whereabouts are you in terms of your company journey? What round of funding are you at? Where are you in your funding cycle? And what are you up to next when it comes to scaling? so I'm not sure what the official number is to be honest but we raced we raced a couple of rounds the latest official one I think is the series a that was done in 2021 or something like that and then we raced a little bit in between and going on to our b fairly soon a little bit active now also a little bit sensitive to talk about that but but and also the least interesting i think but but still i mean we need i would say this i think that um this field in general like brain stimulation for for mental health is a really really interesting field right now we see a couple of rounds some are more relevant than others with like people throwing crazy money because they have a lot of money and then other rounds that are more relevant.

52:13But primarily, I think the results are becoming really, really interesting. I expect this field to... the rounds to get a lot bigger because now there's real opportunity. And there are certain things I can't say on this podcast either, but that would be revealed soon and that I think will push the field even further. So then you can really go up and compete, at least from an efficacy point of view, with the pharma field. And obviously, it's such a much more mature business on the pharma side. And then they have the reimbursement codes ready and everything is very much clearer than in the medtech field.