Neurotech, the Next Frontier: Building, Investing, & Commercial Success in Brain Health, & the Ethical Implications of Neuroinnovation | LSI Europe '23

Transcription

Tonya Dowd  0:05  
It's really great to be here in Barcelona. I've been a part of LSI for since its inception, so it never, it's always just a great event. So PRIA Healthcare just as an introduction is a full service, US based reimbursement, and market access consulting company. We work with medtech innovators early on in the process to really establish and understand the market in the US specifically, and then really develop and carry out the reimbursement of market access strategies. So I'm pleased to be here today with my esteemed panelists. And we're really excited to talk about neuro tech innovation. Just to kind of introduce the topic, there's been an influx of innovation in the area of neuro technology for the treatment, and monitoring of neural disorders, including epilepsy, Alzheimer's, PTSD, and depression, and then to really even enabling movement of a limb through brain computer interfaces, or BCI. So in its simplest definition, neuro technology encompasses all technologies developed to understand the brain and visualize its processes through established modalities such as EEG, functional MRI, or implantation of microneedles. These technologies can even control repair, or improve its functions through methods such as transcranial electrical stimulation, transcranial magnetic stimulation and Bri a deep brain stem or DBS. So the as the innovation in this arena increases, questions around the ethical, commercial and social aspects of these technologies have really come to the forefront as of late, specifically with hope, high profile leaders entering the space with BCI enabled technologies. I think we all know who I'm talking about there. And the emergence of neuro REITs has come into play, which really seek to protect a person's brain and mind. So it's an emerging legal aspect right of these as well. So in our session today, my esteemed panelists and I will explore these issues in more depth and provide their own perspectives, viewpoints and expertise. So I'm going to ask each of the panelists to introduce themselves, Ken?

Ken Mariash  2:24  
Sure. Hey, thanks, Tanya. For leading the panel, Ken Mariash and the CEO of Synaptica Therapeutics, we're developing a non invasive network neuromodulation system for Alzheimer's. Unprecedented phase two clinical trial results better than any drug that at least I'm aware of. And I got a background that Baxter Boston Scientific and consulting before that, right.

Tonya Dowd  2:48  
Thank you, Angela.

Angela Liedler  2:49  
Hi, my name is Angela leader. I'm CEO of PRECISIS is located in Heidelberg. We have invented the world's first minimally invasive fine pacemaker for the treatment of epilepsy patients. It is according to the MDR and CE marked already. Thank you, Anna. And

Ana Maiques  3:10  
Hi Ana Maiques, welcome to Barcelona which is my city. So I'm very proud and happy that you're all here. And you will recognize me if I wear my famous car because otherwise nobody knows who I am. So here it is. These are wireless, non invasive neuromodulation technology called transcranial current stimulation. It also has an EEG and we are in two clinical trials one in epilepsy a pivotal phase three in the US and another one in depression. So we hope that one day doctors will be able to prescribe home use of these as a therapy to deal with brain diseases. Amazing.

Tonya Dowd  3:45  
Thank you, Carolina

Carolina Aguilar  3:47  
Karolina Aguilar, thank you. I'm from Madrid. So you will be aware about the Madrid Barcelona thing, but at least at least case Barcelona adult me. So I'm the CEO of INBRAIN Neuroelectronics. And we develop a graphene based high density and high resolution intelligent neural network for central and peripheral nerve applications.

Tonya Dowd  4:07  
Great, thank you. Great panel here. So the first question I really want to explore and this is a hot topic, especially for this meeting is funding. Right. So it is the focus of this meeting with the promises of innovation in the space and the promises of BCI applications in particular, what funding challenges do you believe are unique to the space as opposed to other disease areas such as cardiovascular ophthalmology, etc.

Ken Mariash  4:36  
I would just start by saying there are challenges but there's also huge opportunities. This is one of the hottest areas in medtech. I mean, we're apart from the Neuralink and Syncron and even the Cognito round there was another company that went public recently in new Mora a lot of companies are getting a lot of traction in this space, device and drug because of the level of unmet needs. as some would call this the century of the brain, and whether it's AI or ml, or BCI, or neuro technology in the brain, I think this is where it's one of the hottest areas in med tech, despite the downturn in funding. It doesn't mean it's easy. There's lots of challenges. But, you know, relative to other spaces in med tech, I think we're one of the hottest spaces, right? If it wasn't, 

Tonya Dowd  5:24  
If it was easy, we wouldn't be here. Anybody else? 

Ana Maiques  5:28  
And I think that, for example, in the Boston area where we raised our first series A I think traditional life invest Life Science investors in the Boston area tend to the to a lot of biotech. Neuro was really hard to raise money. But if you had neuron medical device, I think it was a very hard area to raise money from but I think that in the last years, and I don't think it's only because of Elon Musk canoodling I think there are phenomenal companies like Syncron, and other great companies that are doing great rounds of funding. And I think that's raising the interest of a lot of Life Sciences investors, my main investor in the Boston area is a traditional biotech investor. But he did this medtech and neuro so I hope we can see more and more investors looking into medtech and neuro. 

Carolina Aguilar  6:13  
Yep, if I may add, what is a fact is that one serviceable population is affected and less than 10% get therapy like ours. So there's definitely more budget that needs to go into the development of understanding the brain. And I think it's happening. I am also in agreement with you, we see definitely a change. In our case, we had a lot of support. But even from non traditional investors, like the European Union, has put so much focus starting with a Human Brain Project 1 billion, then, you know, in our case, graphene flagship, and now supporting really, really much entrepreneurship, we have been lucky to actually receive three of the calls that the European put forward for funding, and it's a matter of, you know, having also the ambition to go and get it right. So definitely, there is a change, and we hope to see more so we can address more of the need.

Angela Liedler  7:13  
And I would like to add that I think the whole field of the brain of neurology is a little bit too broad to answer that question. So to my experience, it was quite advantageous that we talked about one neurological disease in our case, it's the epilepsy and the treatment of seizures. So that's a very small, short, but very precise, defined field. And for that, saying that is the fourth most neurological disease then it was quiet, easy. It was never easy, but it was easier to get funded for treatment of a very well defined state status. 

Tonya Dowd  7:57  
A specific patient specific. Yeah, that makes it that makes sense. And

Angela Liedler  8:01  
I think then, disease is the one thing and timing is the other. I mean, I think everybody I think is very scared of conducting clinical studies that that lasts for three, four or five years. And therefore I think it's easier to to have shorter, shorter studies conducted and funded.

Tonya Dowd  8:29  
Great. What are some challenges that were unique in terms of the product development, and even regulatory and commercialization journey that you all have experienced? And what was there any unanticipated challenges?

Ana Maiques  8:47  
Well, I think we have people in the room in the room like Lothar and the TMS, transcranial magnetic stimulation, people in the room. So as an entrapreneur, when you have an idea or a technology, you start with the science, and then you think that the big barrier is regulatory. But once in your regulatory, you start to think about reimbursement or at the same time, and then you see that that mountain is even higher, right. So some people spend more time and money in reimbursement than in the regulatory strategy. And then you have the market access. Right. So I think there are these huge obstacles. Right, and, and with time they change but your we see them as a moving target. Right. So I think that for intrapreneurs in the room, I think that the earlier you start to think about, you know, reimbursement, regulatory market access, partnerships, I think is really important and resources. And I talked about this this morning at 730 in another panel, but resources like the biodesign center in Stanford where they have this consortium of experts that help entrapreneurs navigate those difficulties, I think are super worth it when you're starting and that these advisors, you know, they are paid by the FDA in the case of the pediatric Consortium, or they have been for for my company, an incredible asset right people that have done it before or been there or people from the industry. You In this room that can help you navigate those challenges.

Carolina Aguilar  10:04  
And in my case, we are developing, developing a class three device. And therefore, I find that it's difficult to find the balance between what you integrate on your value chain, what you really do, by yourself versus assembly, suppliers or production suppliers that you might integrate on that chain. And I think it's also a matter of the budget that we are going to be able to raise because I will definitely prefer to integrate a full value chain and control everything also from the quality perspective, and several other aspects. So I don't think yet we have the perfect infrastructure to scale at that level. But I think as the need is there, the budget is flowing. And we are more and more at the talent is also coming. I think we will see also a difference on how do we develop these these products.

Angela Liedler  11:04  
To me, it was surprisingly helpful how the communication with the notified body flew. So we got advice, as you said, we got advice not only around the study protocol, but in the meantime, what happened and they were highly supportive. And I feel these notified bodies here. I only spoke about the EU. God got better and better over the past years. Very helpful.

Tonya Dowd  11:33  
And you've had a lot of success. Yep. Angelyn.

Ken Mariash  11:37  
I would just add that under breakthrough designation, which we have, the interactions with the agency has been very, very good. With a non invasive therapy, of course, the bars are lower. So there's not as many questions around safety. But I would echo you know, what others have said about reimbursement is really the key. And there's this huge disconnect between the drug world and the device world. I've lived in both. And you saw what happened with Ajithelm. and there was a huge uproar over CMS slapping down the entire space of anti amyloid drugs. And then later 180 degrees, they decided to cover Locanda Mab with, you know, very little conditions, and even go as far as covering some of the ancillary services related to the infusion of that drug. So can you imagine you in the device world reimbursement on day one, it's unthinkable in the device world. Whereas the average time that we're out there think there was a Stanford study that said it's about six years to coverage, you would know more than anyone right up to 6 to seven years. So to try to raise money and to try to cross that let that desert landscape in a cash pay environment until that coding and coverage is in place is a huge challenge. And it starts way before you even approach investors, you got to know how you're going to cross that. How's that? How are you going to cross that bridge? We actually recently commented on the TCET, we sent her comments and we pointed out the gross disparity. It's almost like a double standard between the drug world and the device world. And we'd like to close that gap. Right?

Tonya Dowd  13:10  
Yeah, very different processes in the US for drugs versus devices and what Ken's referring to as breakthrough designation with FDA, if you have that for your technology, you have certain reimbursement and benefits that exists today. And then there is a new proposed regulation by CMS called TSET the transitional coverage of emerging technologies that isn't a proposed state. But essentially what it's what CMS is proposing to do for a very finite number of technologies is cover for a certain period of time, pay for and provide coding to specific devices that have breakthrough designation. So again, that is just an proposed state. You just said you submitted comments which the everybody submitted comments. It's a very important rule. But something to definitely watch and think about as you're developing your reimbursement and market access strategy for the US and it is very different in the US. We have a very fragmented, fragmented system, but and I know that you all have breakthrough designation. Congratulations. That's a great, that's a great feat. And, and I you know, if the TSET is, is does go through or just looking at the benefits right now from reimbursement, that from the payment structure, are you intending to get to capitalize on those and pursue those avenues?

Ken Mariash  14:37  
I mean, absolutely, yeah. If there's ever a poster child for the ideal breakthrough for a CMS population to 90% of Alzheimer's patients, that should be no surprise our Medicare beneficiaries, and sorry for the US focus, but that's one of the mind is there was never a better poster child than an Alzheimer's therapy, whereas the drugs cost 26,000 a year and require no MRI monitoring every quarter, and all the testing that goes into the workup that could easily cost 80 to $100,000, your first year on one of those drugs, whereas, you know, our therapy will be a fraction of that with almost no side effects. So I think we have a good chance at achieving that breakthrough designation coverage in the first six months of approval. But if they're only covering five products, that's that's not, that's not enough. They need to go farther.

Tonya Dowd  15:27  
Agreed? Yeah,

Ana Maiques  15:29  
I think we are doing worse in terms of reimbursement. Because when we apply for breakthrough designation, you have this guarantee reimbursement and when Biden came to power that disappear. So that's why I'm saying that is like a moving target and a moving mountain, right, like, so let's see. I mean, I think lobbying in Washington is always a good idea, and people underestimate. But I think that these policies will affect our company. So I hope that we can, we'll take advantage, but I hope they will extend them right in time. Because before he was like, perpetual

Tonya Dowd  16:02  
Yes, yeah at what point would you recommend innovators think about and start strategizing on market access and reimbursement

Carolina Aguilar  16:11  
from the beginning? I mean, also, because you have to answer your investors that are going to ask you that right away. Yeah. And so you definitely need to in your business plan that needs to be figured out from the beginning. Yes, I agreed. And you might not know everything. But that's why we have experts like you to support especially when we are not native from from, for instance, in my case, US. However, you have to understand what's going to be your business model and what you can count or not. And I think we also have a responsibility to innovate. I think by now maybe you know, that I move fears, defense or value based healthcare and how we could in the future paper outcomes are not very devices. And I wish to push that forward in in my generation. So yeah,

Tonya Dowd  17:01  
through a value value based type of structure, versus fee for service. So speaking of outcomes, clinical and economic data are paramount. It's required right for med tech innovators to show and to demonstrate the value of their technology support their claims for all stakeholders, what unique opportunities and challenges and ethical considerations right. Have you thought have you experienced in demonstrating the value and executing these clinical studies?

Angela Liedler  17:35  
But may I start? I mean, the first hurdle is that you need the consent of a patient who is aware that he might be an eligible patient. And in epilepsy patients, that was not always the case, because sometimes there are the parents around. And sometimes there are caregivers around so. And we we set that up quite well with the ethical committees, but we were not allowed to mix children and adults in the very first study. So we had to conduct two different ones, with adults first, obviously, to prove safety and efficacy and only after safety was proven in adults, then we were allowed to jump into a children's study. So it just took time. Definitely it took time and when it comes about the what is the outcome, and it's obvious that efficacy must be proven, but its efficacy, in our case, only reduction of seizures. Is it more is it economic data, is it again, of quality in life, things like that. But we did it very straightforward and reduce it then to just reduce a seizure in frequency. And I think that helped. Yeah, yeah. But at the beginning,

Ken Mariash  19:04  
We have an interesting ethical dilemma. So we're targeting mild to moderate Alzheimer's patients who by definition, are declining, right. So astoundingly, were able to slow the disease by 82%, at least as measured by the primary endpoint, but not 100%. So they continued to decline. And then of course, Sham patients really continued to decline. So the question is, if we enroll a patient at a mini mental state exam of 18, and they declined down to 16, or even 14, that patient is arguably not able to consent. So when we do our flip to open label extension, they can't consent anymore. Now, a lot of these patients have caregivers, so that's great. And then our study will have caregivers but it poses really interesting ethical questions about what point you really have to have the caregiver takeover and, and do all of the sign off. 

Unknown Speaker  19:59  
Yeah, and it seems very specific horse to the disease.

Ana Maiques  20:02  
Yeah, but just to add when I first was approached by a neuro ethicist and they are a number of them that have been working in the neuro tech space for some time, these are mainly academics you know, like unwed lair or current from from Pennsylvania. So I thought that because we're following the FDA rules, we were taking all the ethical issues into consideration. And I was so shocked by some of the questions they pose, one of them was Ana, do your patients whole autonomy and identity and agency when you stimulate them? And I was like, that's not a requirement in any of the FDA trials, right. So I started to get involved in the neuroethics community. And I think if you think about companies like neuro link, or consumer, or I mean, we are all in a very highly regulated space. Right, but I think they're going to be major questions for the millennials. I mean, will you allow a device to be implanted in your brain for consumer use? And does it affect your agency, your identity, or you know who you are as a human? That's why refer us to wants it to be in the Bill of Rights of any constitution, the right to protect your brain. But I think these are fundamental questions. And after what I have seen with social media now with ChatGPT, I'm not super trustful on the humankind. So I don't know, I think that the brain is actually the next frontier. I mean, dealing directly and tapping into your brain, I think, is another dimension. And I think, I don't know if it will be regulated or not, but for sure, has to be oversight and explain to the consumers, I mean, you want to type faster, you want to be smarter, but somebody's going to have a direct access to your brain. It's not like having a social media account that you can disconnect. Right? So I leave it in the room, how many of you would allow an implanted in your brain for enhancement? Oh, we are old, I guess.

Angela Liedler  22:06  
Yeah. Consumers is the one thing probably it's more difficult to answer these questions, but when it's about a DCS, people are far more open. And when are then when they are conscious, when they are suffering, then they're really open to accept things. And I'm a medical doctor, I find suddenly all these regulations, very hard to overcome, but I find they are okay, because they in the original idea was to protect patients, and to not let implants go because you want to accelerate your performance or something like that. But the idea was to treat severely suffering patients. And we haven't a three class three device implanted in heads in in severely ill patients, and once they benefit, then it goes on and on and gets multiplied that the acceptance gets higher over time. So sorry for that, but I'm not completely against putting implants into healthy, healthy volunteers are in whatsoever. So 

Tonya Dowd  23:20  
So maybe it's for purpose. Is it for performance? Or is it really to treat a debilitating condition? Yeah, 

Ken Mariash  23:27  
Okay. But there's a crossover, there's actually a gray area that's, that's upstream of of Alzheimer's or MCI mild cognitive impairment. So in our research, we've shown the ability to increase memory by a substantial amount in healthy normals. So 20% to 30% increase in memory. Now, there's a multi billion dollar industry out there for nutraceuticals and nootropics. It's so called enhance your, your cognition, we actually can do that. So the question is, should we then start to move upstream of diseases and into the elderly patients who want to maintain their brain health, you know, pre MCI, MCI, I could use 20% more memory to so some interesting questions there. Another doesn't involve putting a lead in the brain. So it's a little bit less of a lift, but we are really changing the brain by stimulating it. 

Tonya Dowd  24:22  
Definitely. Carolina.

Carolina Aguilar  24:24  
Yeah, a lot, a lot done. And I know a very relevant neurosurgeon that always says common sense is the least common of the senses. And this means that you know, we have all different values and what is acceptable for you might not be acceptable for me. So definitely, there has to be a guideline that regulates these in a very straight way of what is acceptable and what is not acceptable. And of course, it has to be consistent, consented, and it has to be broad. But there has to be something a benchmark that we will all compare to because otherwise it's going to Be very random, and not protective enough for the human beings. 

Tonya Dowd  25:06  
So So Neuralink just started their first inhuman trial, as I think we all know, would you enroll yourself? Or would you enroll a family member? If you qualified?

Carolina Aguilar  25:22  
So look, I'm going to, I'm going to say something controversial.

Ana Maiques  25:26  
Go Carolina! 

Carolina Aguilar  25:30  
I know the guy is questionable, by he has always delivered on what he promised, right. And we needed a bolt company. And of course, it's easy to to say than do because of course, having 500 million helps. That's how the investment it's going in Neuralink. But I think he's going to get to a place that is going to be opening new frontiers, and is going to take time, I wouldn't take the first generation, I will wait a little bit more. But we are here for difficult and we need to help each other, you know, on the on the COVID vaccine. You know, there's people that said, I'm not gonna do it. But you know, I think we know the ones that we took the vaccine, we were brave, and I thought that I was supporting also the science. And I knew maybe it was not fully tested. And maybe you know, it would have consequences in the long term because it was really not fully tested. It was an epidemiological clinical test. Right. But hey, we went there. And you know, we did it also for the sake of humanity. So I think sometimes we have to take leaps of faith and make this happen. Of course, we also have to regulate, right, like FDA should be on top of Neuralink. Like it's in top of everybody else. Right. But you know, I think if I needed I would that I hope that he will do it if I develop mine.

Ana Maiques  26:54  
Yeah, I think Carolina is right, in the sense that he has put the spotlight into our field. I mean, many of us have been working in neurotech for a long time. Right. But the fact that he entered the field, I think, has raised a fresh interest in that field. And he's phenomenal in explaining what he does. And you know, so I think that overall, you know, we were to the export control conference, I mean, even the government call us all as a field to you know, so I wonder if that would have happened without him entering into the field. So I think he has benefited all of us to have the spotlight in neurotech

Tonya Dowd  27:33  
Are excellent points, Angela.

Angela Liedler  27:37  
Again, I would say, certainly, I would take part everywhere where benefit gets promised or is quite likely to get. I would like to point out something else, I think, to do not harm with any implant is something very important as well, certainly, we do want to bring whatsoever consciousness better or something, but we should prove that we do not harm in other aspects. And I think that is at least as important as doing the next best treatment or outcome. You see, when we talk about the DBS system, the brain stimulations, then they can be very efficacious in whatsoever, tremor treatment or something like that, but they have quite difficult side effects when it comes to mood or so. And I think we should learn from others and not only start from from scratch in every, in every country, so I think the communication and the cross media exchanges is very important so that we can learn and share what we have. I mean, my biggest fear is that we cause whatsoever, depression or something like that, when we do benefit in in the other side of the head.

Ken Mariash  29:24  
Yeah, I mean, it's, it's fascinating. So yeah, if I was locked in, of course, I would want the BCI you know, if I had a spinal cord injury and was partially paralyzed, you know, probably that too. But if I'm just a consumer who wants to enhance myself, I don't know it's a big risk. But it raises questions of you know, we can now use more non invasive modalities to to monitor the brain, and we're learning how to speak brain ish. It takes a lot of ml and a lot of signal processing to be able to understand and deduce what the what the thoughts are coming off an EEG. But if you show a criminal a visual a Have a random house and look at their EEG, you will see a very different reaction when you show them the scene of the crime of the house where they committed the crime. And therein lies the ability to potentially read somebody's thoughts, that poses all kinds of ethical concerns. Of course, that's a criminal, right? But I'm a marketer, I would love to be able to read someone's mind. But as a human, I would much rather that my preferences be inferred and implied not actually read from my mind. So no, I wouldn't sign up for that.

Speaker 1  30:29  
Okay. Do you think that BCI is go against the Hippocratic Oath

Carolina Aguilar  30:37  
it's like everything right in the in the right way and to benefit on health, it is not right. thing, if we start driving Tesla's with the mind, I will be more concerned. But that's why we are talking about frameworks that need to be implemented and enforce.

Ana Maiques  30:56  
Yeah, one of my advisors, I don't know if in the room, you know, this needs who is one of these really talented researchers that work a lot with locked in patients, or so there is people that don't have means to communicate, their brains are intact, and their bodies don't allow them to communicate, I suggest you read this, the what is the diving bell book about the locking patient. So I think that technology in there, if you think of Steve Hawking, or all these people with neuro degeneration or muscular atrophy, that they can their body cannot help them to communicate. It's great, or onward, another great company, right for spinal cord injury. So I think we have hundreds of benefits, but also the press only brings the scary, terrible ones. Right. So I think that there is also a responsibility to show how useful BCIs are being today, right?

Angela Liedler  31:51  
And how safely you can step in, it's only step by step and that is that is good, I mean, we very often we do not have animal models for brain diseases. And therefore, we have to go into humans very early. And then I think the only solution can be do it step by step, various small little steps safety first, then benefit, and then learn from each other. And enhancing cognition is something huge already to make.

Ana Maiques  32:33  
Will enhance in you naturally!

Tonya Dowd  32:40  
Can you speak to the evolution of stimulation modalities to neuro or network modulation? And what considerations are at play for these new modalities?

Ken Mariash  32:51  
Okay, thank you for the question. That was nice tee up. So neuromodulation, to date has been all about you stimulate one nerve, and you get a particular response. Obviously, oversimplifying it, but it's a linear process, right? We are now stepping into a new era of neuromodulation, where it's not about nerve modulation, or even a particular part of the brain modulation, like STN or GPI. Now, we're talking about network neuro modulation. So we're stimulating the default mode network, which has projections to the frontal areas, to the Angular Gyrus to the parietal lobes and the hippocampus. It's a big distributed network, and we're doing it dynamically, we're adjusting, maybe not in real time, but we're adjusting over time to learn how the brain reacts, it shouldn't surprise anyone that everyone's brain responds differently to stimulation. And so we have to titrate that and dynamically respond and evolve over time. So I think we're starting to think more about system modulation, instead of just hit a nerve and get a response. You could apply this to vagus nerve stimulation, maybe if you made it more kind of adaptive, we're getting to see you know, sensory driven DBS closed loop. Now we're seeing closed loop stimulation and Saluda, with closed loop stimulation in the spinal cord. So the point is, we're looking at systems and networks, not individual nerves anymore. And that raises so many questions of complexity, because to read that data, requires ML to get that precision requires target tree to visualize where you're stimulating into sensor response requires very sensitive sensors for what you're doing, and the ability to load all that data into the cloud, and then see changes over time and be able to develop algorithms that drive that that stimulation. So long story short, we're moving into a new era of network neuromodulation is my view.

Carolina Aguilar  34:38  
Yeah, I mean, our FDA breakthrough was a network decoding and modulation so I could not agree more. And it has been a dream since I was little, actually and I was never understanding why we were modulating nuclei, and not taking into account all the rest of the brain and even beyond the brain, right? At the end, we have a central nervous system and a peripheral nervous system. And there are millions of circuits that correlate those two systems. And if we want to really get the full potential of humans in, in healing, I think we need to understand the full connectivity between central and peripheral. That's what we are also doing with the brain, any Neriah, trying to understand how things connect, and how to decode better, and I think it's happening with artificial intelligence in our networks, is happening with chips, neuromorphic chips that also mimic the neural networks. So at the end, I hope that all these understanding of the brain is going to help also other systems.

Angela Liedler  35:46  
I do not like the term stimulus stimulation. I mean, when exactly what you say we suddenly we apply bio electronic pulses into a system. Yeah. And sometimes we have acute and sudden effects. But sometimes it takes months, even years until a modulation gets apparent or gets cost so. And I think when we now come to talk to the public or to patients, and we want to grow patients awareness or confidence in these new therapies, I think we should look for another term, because only a few patients want to get stimulated. Most of them want to get cured or whatever. Yeah. So they don't want it not stimulating and

Carolina Aguilar  36:47  
not deep is also

Angela Liedler  36:50  
and suddenly the term is there. Well, let's change it a little bit to to a better acceptance impatient. 

Ana Maiques  37:00  
Yeah, one thing that we are trying to do a new relate to this, and I hope we succeed is building these, we call them neuro twins, but these are computational models of the brain in the cloud. So instead of stimulate, can you simulate? So instead of using the human as a testbed, can you just do it in the cloud, understand how the brain works from an electric perspective simulate? So you have Alzheimer's? Who How would you respond to this? So I think that that would apply also to the drug world, right? Like before you prescribe and then come back in three months? And let's see, I mean, can we use artificial intelligence, for the good use of really simulating the response of the brain to different treatments and personalized in ways neuroscience hasn't been able to do before because it's so difficult.

Carolina Aguilar  37:47  
Yeah, she she's building an amazing model. I'm such a huge fan of that work. It's hard. So anyway,

Tonya Dowd  37:55  
We definitely have some evolution here. And not only in the terminology, but just the whole arena. So this has been great. We're almost out of time, believe it or not, I'm going to ask each of the panelists to just give the audience a quick couple of key points. Carolina, start, please.

Carolina Aguilar  38:14  
I think as entraprenuers were here to do difficult, right. So our responsibility is to push the next, the next frontier of neuro tech for the well being of humans, and we are all going to be patients. So I hope that you all progress. And help me when I'm, you know, you see me all. So yeah, that's my message here.

Ana Maiques  38:36  
And I think in my case, we are preaching, you know, to every kind of audience, but I would love the healthcare system, and in general, the bio world to understand that they may be new ways to deal with brain diseases other than drugs. And you know, in the Egyptian times they used to take fish from the river and put them on their head to deal with pain. So the concept of electricity in our history has been there since the Roman times. So I hope that we are companies will be able to show to the world that there are other novel ways to deal with the brain because patients are suffering and what we are delivering today is not enough. So I hope we succeed.

Angela Liedler  39:17  
My sentence or advice would be if you are an entrepreneur, if you are a start up, then talk to your notified bodies, talk to your as early as possible. It takes years until they until they understand what you're doing and what you want to achieve. But once you have them in your boat, then then it's good. But it takes a long time.

Ken Mariash  39:48  
Just parting words. I think we're entering a really fun time, an exciting time where we're going to see neuro tech development start to encroach upon drugs and you see this with like setpoint and vagal nerve stimulation, it's the biggest class of drugs, the anti TNF alphas. And setpoint has a therapy that can really rival those. And we're starting to see that in other areas of neuro tech to, you know, not just not just Alzheimer's, but we're starting to see them one by one sort of those two worlds collide a little bit. And so bioelectronic medicine is one way to think about it's one term. But, yeah, fundamentally, I believe that the frameworks for reimbursement as I said before, there needs to be some equivalence there because it is a double standard between the device world and the drug world. They need to come together

Tonya Dowd  40:38  
and start the reimbursement planning early.

Ken Mariash  40:40  
Absolutely. Yes.

Tonya Dowd  40:42  
Thank you. I want to thank everybody in the audience for attending. I was this is a great conversation. Thank you to all the panelists. So excellent dialogue and excellent points. So thank you. Thank you.