Neuromodulation: Hurdles, Ethics, and Unmet Needs Driving Innovation and Investment | LSI Europe '24

Ana Maiques 00:00  
Hello everyone. Thanks for coming to our panel. We are very excited to be here. My name is Ana Maiques. I'm the CEO of Neuroelectrics, and I'm very honored to moderate this panel. We have two investors and two startups or companies or entrepreneurs, and I'm going to let each one of them introduce themselves to talk today about challenges, ethics, and unmet needs driving innovation and investment in neuromodulation. So, you start. Balint, thank you.

Balint Varkuti 00:36  
Thank you very much. My name is Balint Varkuti. I'm the CEO of CereGate. CereGate is a startup founded in 2019, and we built a brain-computer interface that is capable of sending information into the human brain through implantable classic neuromodulation systems such as DBS and SCS. We focus on movement disorders and a number of other interesting indications with this unique technology.

Catherine Poulin-Filion 01:00  
And I'm Catherine Poulin-Filion. I work for Sectoral Asset Management as a principal, and we do investments in biotech and medtech in later-stage companies.

Melissa Lezameta 01:11  
Melissa, I'm an associate at Epidarex. Epidarex is an early-stage investor. We have offices both in the US and the UK. In the US, we tend to invest in underserved areas. In the UK, we invest all over the UK in early-stage companies, so seed and series A typically, and we do both therapeutics and medical devices.

Meron Gribetz 01:34  
My name is Meron Gribetz. I run a company called Inner Cosmos. We build a brain-computer interface for depression. Here it is. It's tiny. It's the smallest BCI, and it provides neuromodulation, both read and write, for a number of mental health disorders.

Ana Maiques 01:53  
Well, it's great to have you all. So, you know, as the name of the panel says, challenges. So let's start with the challenges, and all of you who are attending LSI, we know fundraising is a big topic, so let's get right to the point. I would like Catherine to start to answer, you know, in terms of as an investor, in terms of funding neuromodulation companies, why do you think that maybe neuromodulation companies have been more resilient? And I know you have a particular view also on the clinical data when you are dealing with investments in neuromodulation. So tell us a little bit about your perspective and the framework of investing in neuromodulation and whether you are positive or not.

Catherine Poulin-Filion 02:34  
Absolutely. So I think when I take a step back and I think about innovation, you can either innovate for a large number of people and innovate, let's say, marginally, or you can also innovate for a smaller number of patients or people and contribute significant innovation. And in neuromodulation, we're very lucky because you can do both. In that case, we basically see that there are a number of levels of innovations that we've seen across the years. We really started with spinal cord stimulation over the years, and more recently, we've seen a divergence. We've seen a bunch of sub-indications. So I'm very, very positive about neurostimulation overall.

Ana Maiques 03:26  
And why do you think it's more resilient? So that's one of the things that you have in mind. Why do you think the field is more resilient than others?

Catherine Poulin-Filion 03:33  
Well, it is because of that large innovation for so many different patients. And this yields massive markets, and the patient impact is very important in that case.

Melissa Lezameta 03:50  
Okay, if I could add to that from a more mixed investor perspective, because we do, again, both therapeutics and medical devices. For us, in a risk-averse market, medical devices also have disadvantages, right? So we've seen, like, in the last few years, both neurostimulation and cardiovascular have both been very resilient, and they both have in common huge areas of need. Oftentimes, the indications related to neurostimulation are also related to age in some cases, like Alzheimer's or bladder issues. So for us, the potential that you're seeing, but also for us as investors in a risk-averse market, in a way, it's a little bit less risky to invest in these medical devices than in therapeutics. So we think that's also made it resilient.

Ana Maiques 04:42  
So now we have the view of the investors in the panel. What about the companies raising money? So Meron, do you want to start?

Meron Gribetz 04:50  
Yeah. So if we look at neuromodulation as a category, and then you zoom into brain-computer interfaces where Balint and I work, we have Elon Musk to thank for some resilience in the markets. Over the last couple of years, he invested in Neuralink, and that became sort of widely understood and known by the general population. LPs, our general population, they put pressure on VCs. And then here we are. And that's kind of an interesting side note.

Balint Varkuti 05:23  
So I think as far as we enjoy Elon's presence and the fact that he put a spotlight on brain-computer interfaces, it is a mixed bag in many aspects. Because also, if you trust the secondary level valuations that they discuss currently for Neuralink, then it's larger than the DBS and SCS markets combined, which have been around for 30 years. So in other words, a lot of expectation is being created, and I hope that all of this motivation and this drive will not only survive market release and the first patients, but that then we get to branch out and really serve multiple aspects of this community, indications we have not served so far. And so I think that is fantastic. A rising tide lifts all boats, very much. But the real challenge is, I think, going to be in the next cycle, once the first market release has hit, and then how do we differentiate? How do we position ourselves to really maximize benefit for patients, payers, and investors?

Ana Maiques 06:26  
Great. So I think that, as you can see, we think that neuromodulation is a hot topic from the investment and the company side. But what have you seen in terms of innovation? Because, you know, I think LSI in particular has been exposed to medical technology and neuromodulation for years, right? And you're, like, very active in the front line in your field. So we can start with Melissa. But Melissa, where are you seeing in terms of innovation that you think you're really excited about on the neuromodulation side? I mean, what part of it is new with the new technologies that we didn't have maybe 10 years ago?

Melissa Lezameta 07:00  
Exactly. So, aside from all the new indications moving into, yeah, we've seen things that are now implementing, and you can probably talk to this much better than I can, Ana, but you know where you used to just target one single node, now we understand that a lot of indications are a lot more of a network complex problem. So moving that strategy from targeting the connection between networks rather than a single node, micro-modulation, and learning over time, so implementing machine learning and making that adaptable not only to each patient but also within the patient, to the different spatio-temporal needs of that specific patient, right? And I think that's something that, I mean, that point specifically, compared to therapeutics, has so much potential, right? I mean, therapeutic to therapeutic, you give it, it either works or it doesn't, but you can tailor it. And so having that in special indications for neuromodulation, it's really high potential, and we love seeing that. And like, just as an example for epilepsy, right? I mean, we have therapeutic epilepsy companies in our portfolio, but like, one thing that we can't do, you know, right now, is detect the seizure before it happens. And so with neuromodulation, you will dose specifically when and as needed, so you don't have all the systemic effects that you're going to have with the therapy. So that personalization is huge for us. And then, like, other things that we look for are new biomarkers, so that you can start seeing the patient response to the stimulation or not. And capacities that we're seeing now is also the ability to reprogram, either remotely from the physicians that are controlling the patients or even at home, you know, for the patients themselves, who can then reprogram their stimulation based on their own needs. As I said, like, depending, for example, on pain, if they're more in pain one day, less pain another day. And then, of course, there are a bunch of other things; those are the main ones for me. But then, like a lot of other things, like new materials that adapt to the flexible nature of the brain, the battery life, making things that are MRI compliant. So I think bringing all of these things together is what's really going to make an impact. So one thing that we are seeing is that each company is usually good at one thing, or maybe solving two of these problems. And I think that when companies, as this area matures and progresses, and we start seeing more partnerships between the different startups, we're going to see things that are really impactful because they'll bring all these technologies together.

Meron Gribetz 09:45  
Yeah, if I may add on to that. So the personalization aspect is absolutely key. For a very long time, hardware was basically the only value-driving path, right? You had to have the right electrode or the right encasing, the right MEMS, the right soft electronics technology. But now there are other things that are more related to software, to artificial intelligence, which obviously has a hype moment. But if you look at it, I think if you look at all the implantable devices per year, which is north of 100,000 alone in neurostimulation, about 400 to 500 man-years of personal hours are spent programming these devices, which is unreimbursed. It limits the ability of the neurologist or the practitioner to treat many patients. So we, for the first time, have a moment where we also have to think about the key. If we want to scale these devices, we have to make them very intelligent, self-programming, and smart. Adaptable. And I think this is a new competitive field that is going to really improve the outcomes.

Ana Maiques 10:39  
Now, if I can piggyback on that, I kind of see it as there are probably more ways to cut this, but what we've been referring to is using, let's say, an indication when there's already a solution and making it that much better because of technological investment. There's comfort, I think, in investing, let's say, in medtech because there are so many learnings that we can have from the tech industry that we can now finally actually bring into the devices. Here I'm thinking computing power, edge computing, better sensing technologies, smaller batteries, etc., making implantables that much easier to implant and safer to implant. I'm also seeing still a lot of opportunities in these white spaces where neuromodulation is still only competing against drugs. I mean, we have three portfolio companies that are in the neuromodulation space, and they're all within that category of white spaces. If I think, let's say, of Nautrix Health, which has a neurostimulation device for Restless Leg Syndrome, their only competitor right now out there is dopamine, which, over time, augments the disease state of the patient. That's not a very good value proposition. So we're still seeing some opportunities in these white spaces as well.

Catherine Poulin-Filion 11:59  
Yeah, I think that before I leave it to Meron, I think that it's really interesting. I was in Boston last week at a couple of conferences, and we were discussing how the healthcare system, for example, in the US, is so overloaded, right? One of the things that was said is we will only bridge that gap through technology because there is no way in which there are enough physicians to attend to the demand in many cases. So I think that to your point, right? Medtech and tech, I think, are part of the reason why we can maybe provide solutions that are going to make the healthcare system much more efficient than what it is. And AI, we haven't talked about AI, right? But that's one of the things that maybe Meron you can talk about what innovations you are seeing as well in the brain-computer interface space.

Meron Gribetz 12:47  
Sure, absolutely. We're working with Balint's framework of both the ability to sense the brain and stimulate the brain in a closed-loop fashion. So there's a sort of a core tenet now of where brain-computer interfaces are going. In our case, there are established therapies in depression, like transcranial magnetic stimulation, that have immensely high efficacy, but you have to spend a month, say, in the hospital. So yes, we can be a therapeutic. We could stimulate and we can get people out of depression chronically from the comfort of their home. But what's interesting here is that we could also sense the brain for the first time and build your depression graph, closing the loop, allowing psychiatrists to see an order of magnitude more patients by just looking at their laptop at their depression graphs of so many patients to your point earlier. And so I think that the closed-loop AI-based recommendation engine we're working on for psychiatrists is kind of like a core tenet of innovation. Broadly in the space, I see three logical phases. One is companies trying to close a loop with the clinician doing remote programming or in-office programming. That's kind of cool. And then there's the remote AI assistant that can sort of support their decision-making process. And then as a third stage, there's micro-closed loop, where millisecond by millisecond, the algorithm can actually stimulate far better than a physician could. So you have these phases of how this innovation may progress, and I'm curious to see how the broader industry follows them.

Ana Maiques 14:25  
Yeah, I think it's very exciting because if you think of something like depression, one of the things that we've seen in a lot of neuromodulation conferences, if you think of big diseases like depression or maybe Alzheimer's or neurodegeneration, it's so huge that there are talks about this neurocircuitry approach in which you can maybe link symptoms to specific circuits of the brain. So there is so much we don't yet know about, for example, depression. I mean, if you have anhedonia or a mood disorder symptom, different circuits in the brain may be affected. So if you can map them and stimulate them, you're really personalizing in ways that were impossible before, and that's why I think it's the beauty of neuromodulation or medtech, right, where pharma cannot get right, where you can really have this level of tailoring that is amazing. So that's great. So we had discussed a little bit about Elon Musk, and of course, I agree with you that he brought the spotlight. So even if you like him or not, I think that for the companies raising money, this kind of "me too" Silicon Valley, I want to be Elon Musk, is driving a lot of funding into companies, right? But after all the debate with social media and the elections and things like that, I mean, the next frontier of having an implant in your brain ethically is a new ball game, right? Tapping with your brain, you know, that's what makes us humans. So I would like maybe Meron to start by, you know, what are the ethical consequences of implanting chips? And none of us in this room, we are millennials or super young, but I am not sure the young people think the same way as the people in the room, whether it doesn't matter that somebody plants something in your brain forever and ever. And so what are your ethical considerations with, you know, neuromodulation, specifically brain-computer interfaces?

Meron Gribetz 16:13  
You know, I took a bottom-up approach on this, and I read a lot of internet forums over many years to try to figure out what the world thinks, and then to try to figure out what I think. I grouped the broad ethical questions because we're dealing with the Holy of Holies of the organ that represents our identity. And so the three categories that I found are most interesting for people to discuss are identity, what makes us human, our agency, and privacy. So agency: am I going to be controlled somehow, remotely, by some faceless company, or worse, a company with a face that we don't all identify with? And am I going to, from a privacy perspective, you know, again, this information is so critical and holy, particularly for brain-computer interface companies that are sitting over the motor cortex, sensing the movement of your perceived, imagined words in your head and transcribing it to a computer. What does that mean in terms of the privacy of my internal chatter? And in terms of identity, it's like, when do I lose my humanity? At what point am I so augmented that I'm not yesterday's Meron? So all these questions are super interesting to us, and I spent a lot of time thinking about them.

Catherine Poulin-Filion 17:33  
So this aspect of privacy is incredibly powerful. So brain-computer interfaces, especially how they work today, sense of movement, intention, right? And so I might have the intention to grab the candy bar, but I'm not acting on it. But if the device can detect this and writes a little note that I wanted the candy bar, if someone else gets their hands on this data, this is really powerful stuff. So I think we are very far away from mind reading, as we see it in science fiction. But there are true consequences to annotated or tagged data that we currently try to record to make the therapies better. The more we know about how these people's lives are at home, for example, to do a depression graph, the more we know about these people, period. So this is a very, very interesting new aspect that we all have to grapple with. And I think the other aspect is, as we are both doing implantable BCIs, is the surgery appropriate? So today, no one is going to get lifestyle surgery or cosmetic brain surgery to get a BCI to control their Tesla. Today, it is still an invasive approach that has infrequent but potentially serious consequences. So I think there's a lot of talk about this in the media, and sometimes investors have the wrong idea. They think, okay, I'm just going to get this tomorrow in a boutique experience. I'm going to lie down, they're going to do it for me, and it's going to be wonderful. So this is another aspect that we have to be careful about what expectations we generate, and we would also have to be cognizant of the fact that the technology is advancing. So the cortical sewing machine that Neuralink uses is a remarkable piece of technology, probably not the way everybody would choose, but it's one step. As we really make the surgery more accessible, and like cosmetic surgery came out of burn victim reconstruction, we will see the event where cosmetic brain surgery is going to become a possibility. And we don't have a large conversation about this in society yet, and we should.

Ana Maiques 19:35  
Yeah, and before I let Melissa and Catherine speak, so in the room, how many of you are okay with an implant in your brain if it's not for medical purposes, for example?

Meron Gribetz 19:49  
Almost like you can do a better job selling the upside. How about 20% more cognition for all of the investment activities that you can do, giving you an edge? No? Okay. -- I don't believe that my nine-year-old is already counting on having.

Ana Maiques 20:04  
That's what I'm saying. I think that generation and then how many in the room think the government should step in regulating brain-computer interfaces, that they should be regulated by governments?

Balint Varkuti 20:18  
Why? Okay, yeah, now the boldness, so it's already happening. So there was an export control meeting of Congress last year in Washington, and I was there. Yeah, so certain BCI technologies are already being discussed not to be exportable into certain countries. So, but is that really a threat? Is probably another conversation.

Catherine Poulin-Filion 20:39  
I was in a panel on AI for good in Geneva. And I thought it was all about, wow, AI is going to do good for humanity. And I realized that, like, it's the other way around. Like, all the governments were looking at the trends to go on regulation. So it's like, sometimes you go to conferences, and it's not what you seem, you know. So now there is a neurotech track in Davos, which you also think is good, but it's all leading to regulation.

Ana Maiques 21:08  
You mean to pitch that?

Catherine Poulin-Filion 21:10  
It's needed, right? Because legislation and regulation are always behind technology. So, like, I mean, you have to move it at some point. And even though we're very optimistic about this, I think you have to start thinking ahead of time about the potential risks because it is going to take a long time to then implement the regulation.

Meron Gribetz 21:28  
Yeah, absolutely, especially that now the risk-reward calculation is a health issue versus all the challenges that we've just discussed. But later on, this will evolve.

Ana Maiques 21:41  
If you would have to make predictions about, let's say, where we are going to be, let's say, 5 to 10 years from now in neuromodulation, right? So what would you wish to see out there in LSI, right? Presented here like success stories. So let's start with you, Meron.

Meron Gribetz 22:01  
Well, I'm biased, so I would imagine that in I'll zoom into brain-computer interfaces to answer that question, and then maybe riff a bit, but there'll be less invasive interfaces that provide—there's always this balance between risk and resolution that we're grappling with in this industry. You know, the networks that we wish to modulate, and the success of neuromodulation lately is because we're targeting millions of neurons at a time, not single neurons at a time. That's where we address paralysis. So that's where you're moving a robotic limb. And so the higher the resolution you need, the more you need to interact with singular neurons, the more invasive it is, and society is going to have to be okay with a craniotomy that penetrates the inner table of the skull, cuts the dura mater, the protective sheath around the brain, and potentially puts a sewing machine in the brain. I mean, this is incredibly invasive. I don't think we're ready for that in the next decade or two, I think, for very narrow cases, for people with full tetraplegia, paralysis, perhaps. But I think the first bridge that we're going to go through is sort of this mental health where there's huge need today, as we know, number one killer in many countries of much of the population. And so the next one is really higher resolution interfaces that are in the brain. And then it might even get more intimate. You might have genetic modification type brain-computer interfaces that interact neuron by neuron for other indications, like memory. And so I think there's lots of action in the neuromodulation BCI, and we're just at the very beginning of it. And I think things that don't penetrate the skull will succeed first, then will penetrate the top of the skull, and then we'll be in the brain.

Catherine Poulin-Filion 24:10  
The thing is, I think the non-invasiveness is going to be a really big deal. And so we could find—and again, I think we just need to keep innovating and keep looking for ways to get that deep penetration without actually having to have the surgery, if you can, right? So, like Parkinson's right now, it's really deep. You can't go in there. It's like from the outside. But if we can find a way to either amplify the signal or get in deeper, but targeted, and people are very creative about these kinds of technologies. I mean, seeing it applied in other indications with other modalities in which you think something can't be done, and then all of a sudden there's this breakthrough, like, oh yeah, now we can do this because we really amplified this in imaging. And, you know, things that we can image now that we couldn't image before just because of this signal amplification. So I think if we can have learned from other technologies too that are completely non-related to this and improve that non-invasiveness, that's one. The other aspect, while things are still invasive, also, if we can improve on the surgery side, right? Because there's the risk of surgery, but if you look at it from a different perspective, like this is the safety of the surgery itself. But then once you've got everything in place, in a way, it's a lot safer than therapeutics because you get that instant readout, right? So if your dose is too high or you're in the wrong location, you're going to see that immediately, and you can modify that. Whereas with a therapeutic, you could just have to stop treatment basically and deal with the aftermath. But if we can just make the surgery safer and improve that, and again, we need to bring in other technologies in addition, right? So to me, like that collaboration between different companies and different partners is really key.

Meron Gribetz 26:00  
When you touch on a good point, the aspect of being minimally invasive over time and even non-invasive over time, but for the targets that still require surgery, better materials and better transmission of energy as well, or you could stimulate with a different type of energy over time.

Balint Varkuti 26:24  
Yeah, so there are multiple converging trends why the surgery has to get better, and we are lucky that we are basically riding that wave. There are tumor modification agents that are brought into the brain through convection to enhance drug delivery to kill GBMs or other types of tumors. There is microsurgery of vascular nature. There is neuromodulation implantation. There are BCIs. So there are many incentives for hospitals in the future to have a minimally invasive intervention room that focuses on these procedures that are not necessarily life-lengthening, but they give quality of life back. They return people to work life. They return people to living a fuller life. And so that is a very nice trend, I think that we've seen that is going to definitely play out in the next five to ten years. The other aspect is consumer technology is going to correct some parts of the BCI tree that probably don't live very long. So, I mean, the Apple Vision Pro can do eye tracking very well. And sometimes eye tracking is good enough for people with paralysis to do certain things, both in terms of bit rate and in other aspects. So as consumer tech gets better, some of these use cases probably lose their USP, and we focus back further on, if we do the surgery, we really do it for a very good reason, for example, high bit rate transmission, and that's one of the reasons why we chose an invasive route because you can't transmit information into the brain through non-invasive means at the bit rates you need, for example, to create an artificial sense of balance or hearing or these types of things. But I'm very optimistic that, basically, both the market will correct and that the trends are going in the right direction that ultimately will allow us to serve people better.

Meron Gribetz 28:06  
Yeah, just quickly on this one thing I'm actually very excited about, though, with the technology we currently have, there are still so many indications that we can go after with our current technology and that we just haven't found yet the targets. So we've discussed kind of the 10 to 15 year out. But I think the future is very bright, actually, for neuromodulation in the next five to seven years. There's going to be many indications going to be well served.

Ana Maiques 28:35  
Yeah. So we have a brave person in the third row that is going to ask the question, so big clap and go for it. Thank you.

Audience Question 28:45  
So I'm in the ophthalmology space, specifically in retina, which is the first organ to the brain. So I'm wondering, is the eye an entry point where we can do these therapeutics rather than going into invasive surgery?
Where retinal specifically, there are companies now that can use the image to do early detection of Alzheimer's.
So there's a clear indication. Thank you. My question is already over.

Ana Maiques 29:19  
No, we heard you, but continue. 

Audience Question 29:34  
That's it, I just want to know, have you looked into the eye as a way for the therapy to go through? Maybe it's light stimulation. Maybe there is some sort of wave we can just put in through the eye rather than having to do a craniotomy.

Meron Gribetz 29:34  
So I can answer that. There are many diagnostic approaches that, for example, look at the eye both in terms of pressure and in terms of other aspects, basically as a window to the brain. So both in terms of what is the pressure in your brain, as well as certain signs that might indicate degeneration or dementia. So both are becoming more interesting as diagnostic tools. There are multiple startups that are trying to use light wave patterns that are supposed to destroy the progression of, for example, Alzheimer's disease. There is a company that also in the optoelectric space that tries to do genetic modification and then basically give people back their eyesight, which is very tricky because you have to release the agent that you inject that does gene modification in a human, so that has certain hurdles. But on this front, there is something happening. Generally, the idea of using sensory conduits to the brain as the interface instead of going into the brain is, by the way, exactly what we do. So we go to the nerves that lead up to the brain instead of having to open the skull. Because, as you say, that is less invasive. And the brain, just when we're babies, learns to interpret our own senses; it also learns to interpret additional signals sent along the same information highway. So in short, there's a lot of innovation actually happening exactly in this space.

Catherine Poulin-Filion 30:55  
And one example, my investor in our portfolio of companies, there is a company in the US called Cognito Therapeutics, which is Boston-based, a spin-off of MIT. In the preliminary MIT studies, they saw how flickering lights at 40 hertz were reducing the amyloid plaque in Alzheimer's patients. So now they're in a phase two of 700 patients to really show how after one hour of flickering light, they have some glasses if they can sustain the effects that they saw in the rat. So the jury is out there because they're in clinical development, but it's an example of how there are companies that are using the eyes as a therapeutic way into the brain.

Meron Gribetz 31:36  
So probably it's a good segue to talk about clinical data in general. So clinical data obviously has a large relevancy in getting approval, but I think you also have to get some after you've got it.

Catherine Poulin-Filion 31:47  
I think Katherine had some very good points about how startups are getting clinical data and for what, right? She mentioned, but I think that are we getting clinical data only for FDA approval, right? Is it for marketing? Is it for fundraising, right?

Catherine Poulin-Filion 32:01  
Oh, absolutely. So, as I mentioned before, there are different types of positioning, right? Either you're entering a new white space or you're innovating within an existing space. But if there's a large target population, there's a tremendous opportunity to invest in that business long run, and clinical data is part of that. So we see a lot of companies that are focusing on clinical data as a means to get to regulatory approval, but we see it as much more than that, where if you have that type of opportunity, you want to build your moat around it. You want to build the distance with your competitors as well. You want to be able to make arguments to reimbursement agencies and to physicians and to pitch as to why it should be your technology that gets utilized. Oftentimes there are some things that can be done while designing a pivotal trial. For instance, I can incorporate some data points that may not be asked by the FDA or by European regulatory bodies, but that can be useful down the road for reimbursement conversations. And these should really be integrated.

Catherine Poulin-Filion 33:21  
Yeah, so if you only start looking into the value-based healthcare data that you need to argue for the right reimbursement level when you get FDA approval, you're already too late. You're right in the valley of death. And then good luck. But many people, or many companies, have realized this much earlier now and take this into greater consideration.

Catherine Poulin-Filion 33:37  
No, absolutely. In the past, I'd say, seven years or so, we've seen more and more startups having conversations with reimbursement consultants earlier on and incorporating the feedback while designing their pivotal trial. And we're starting to see, you know, the fruits of that as they're getting FDA approval and starting commercialization, and they're having better conversations with reimbursement agencies.

Catherine Poulin-Filion 34:02  
Yeah, and the FDA has the TAP program, which is attempting to sort of structure that and provide resources early on for us on reimbursement. So there are numerous attempts at that.

Catherine Poulin-Filion 34:13  
And the new program for transitional reimbursement that is currently being discussed, I think, in the Senate. So that gives a lot of companies hope that breakthrough designation might be tied to four years of a period where you can build out the proof, and I think that would be good news for everyone.

Catherine Poulin-Filion 34:27  
Yeah. I mean, my company got breakthrough designation right when the Biden administration began. So we are really keeping our fingers crossed because I think that it's so hard. I wish they would be more aligned, CMS or the payers with FDA, because the fact that you have to go to these two different windows—before you had breakthrough designation, you had automatic reimbursement, which was awesome for startup companies, but I don't know if it's going to happen or not. There are a lot of talks, but in any case, it should make it easier, especially for with the safety and efficacy profile, you know, where the need and the safety I'm working in epilepsy, where these treatments don't have options, and it's non-invasive, so really have to go through all these hard to learn years and years while the patients are waiting. So there is no sense of urgency out there, right? So anyway, I want to thank all the members of the panel. I think this was super exciting, and I don't know, Melissa, if you want to have any final remarks.

Melissa Lezameta 35:25  
Yeah, no. I mean, as I said, I think I just repeat myself, we see this as a really, really exciting area. We look into investing in new indications, like Catherine said, and just see more of the non-invasive. I think they can really, really make a difference. Personalized therapies, especially like epilepsy, is a really big area for us, and children's epilepsy is the real need, so that's one that we're really hoping to see some technology. And so, yeah, we're very excited.

Ana Maiques 35:57  
Big applause for the panelists. Thank you very much. Applause.