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Bruce Leuchter: CEO of Neurvati Neurosciences · BioBoss

• 0:00
  John Simboli: Bruce, welcome to BioBoss.
• 0:02
  Bruce Leuchter: Thanks, John, pleasure to be here.
• 0:03
  John Simboli: Bruce, what led you to your role as cofounder and CEO of Neurvati Neurosciences?
• 0:09
  Bruce Leuchter: It draws on a number of different experiences that I've had over the course of my career. And, you know, I grew up in the home of a brilliant clinician-scientist neurologist, found my way into neurology residency, then did some training in psychiatry, because I felt like I was getting half the story. So doing both neurology and psychiatry broadened my horizons around thinking through issues related to the brain and nervous system.
• 0:32
  Bruce Leuchter: And from there, I believed that understanding industry, and as part of that, financial services in healthcare and biotech, would create another dimension to the work that I had done to date, but use the scientific and clinical perspective, and frankly, my love of those two dimensions of my life, the scientific training and clinical experience to inform how I performed my role in the financial services sector. And it was always a third leg of the stool to be able to leverage all of that in actually operating a neuroscience-focused biotech company. I think there's no greater privilege beyond, perhaps, taking care of patients that one can have than developing a novel therapy for a disease with high unmet medical need. And that is our mandate at Neurvati, and we get to do it with best-in-class sponsors, financial partners who help us along the way. And that's ultimately what led to me sitting in this seat, which, as we'll talk about, I'm sure later on in the discussion, has some unique features to it that draw, in particular, on the number of different professional experiences I've had over time
• 1:46
  John Simboli: When you were thinking about that, how you would apply your background and your interest in, and seeing how it could turn into, perhaps, a therapy someday, you must have looked at a lot of different options and a lot of different possibilities. How did you land on the one that enabled you to become the co-founder?
• 2:06
  Bruce Leuchter: Well, I think we in biotech often find ourselves looking across the landscape of opportunities. And in many cases, particularly in the venture world, you find early stage science, perhaps coming out of a top tier academic institution, or pre-clinical assets, molecules that are in development, pre-clinically that haven't yet found their way to the clinic. And then you work your way downstream and find clinical data sets around which you can organize for opportunities that exist in the market. And for our investors, Blackstone Life Sciences, the clinical data is really important, and it's important because we focus our efforts on mid and late stage drug development, where often companies find themselves in various different circumstances that preclude progressing programs internally and require externalizing those programs, putting them in the hands of entrepreneurs who, in our circumstance, have the necessary amount of capital to finance, they've been in late stage development. So for us, while there is a ton of raw material out there, early stage technologies that hold a tremendous amount of promise, our mandate is one where we need to look at mid and late stage development, and there are some unique challenges associated with that. Neuroscience is a space that has a pretty significant capital requirement to develop drugs through approval. Timelines can sometimes be more prolonged than other therapeutic areas, and risk is quite high. And it's not without understanding all of those things that people make decisions around neuroscience, product candidates, and for us, focusing on that later stage of development where we can organize around data, clinical data and pre-clinical data that give us conviction, is critical to getting a new affiliate co over the finish line and in our first affiliate co, GRIN Therapeutics, that fact pattern existed. We had a molecule that had a significant amount of clinical data, had a whole lot for us to look at in terms of safety, tolerability, dosing, protocol, PK, and even data in certain neuroscience indications. And when we coupled that with GRIN related neurodevelopmental disorder and knew that we could use human genetics to identify the most appropriate patient to enroll in our study, and combine that with the dossier that we had around this program, it made a whole lot of sense to push off on this particular opportunity, and we've been at it now for four years.
• 4:35
  John Simboli: Does your work put you at the head of GRIN and Neurvati?
• 4:40
  Bruce Leuchter: So Neurvati Neurosciences is an operating company, a development company that is owned by Blackstone Life Sciences, and it was created to work on neuroscience therapeutics across the waterfront, which means that we're not restricted to a particular vertical in neuroscience. So as an example, right now, GRIN Therapeutics is focused on neurodevelopmental disease, but we look at opportunities that are in the clinic with critical mass data that could be in the neuro oncology space, could be in the neurovascular space, neuromuscular space, neuroinflammatory disease space, neuropsychiatry, pain, sleep, wake. All of these verticals for us are options, and the lowest common denominator is whether or not there's enough data to support a highly convicted view around success in mid and late stage development and regulatory discussions. So what Neurvati does is operate those affiliate co's, and that's where the people sit, the human capital, but all of the action, or activity, if you will, exists at the affiliate co level. The Neurvati team drops down into that affiliate co and executes.
• 5:50
  Bruce Leuchter: So all of the functions that you'd ordinarily expect to see within a biotech company certainly exist. They exist at the Neurvati co level, and then the day-to-day execution occurs in the affiliate co. And that's where the asset sits, that's where the capital flows when we raise capital. That's where the governance sits, where the incentive structure sits. And it allows us, as Neurvati, to continue to progress this sort of work across a number of different projects going forward. But the project that we have in hand right now, that we're solely focused on is GRIN, GRIN related neurodevelopmental disorder, and the development of radiprodil to treat these kids with a really difficult and highly morbid disease process.
• 6:36
  Bruce Leuchter: When we look at opportunities, we are focused on human genetics. We want to have clarity around the patient population that suffers from the disease, how we can identify those patients, definitively diagnose those patients, and deliver precision therapeutics to those patients. People define precision therapeutics in various different ways, with various different therapeutic modalities. But the bottom line is that we're aiming to use human genetics, biomarkers of all sorts, whether they are from the cerebral spinal fluid, whether they are imaging biomarkers, electrophysiologic biomarkers, to try to triangulate around the patient population that is best suited to enroll in a study and to potentially benefit from an experimental therapy, should it get approved. And that's exactly what we did with GRIN. We said there's a genetically defined disease in GRIN related neurodevelopmental disorder.
• 7:26
  Bruce Leuchter: There are no drugs approved to treat that disease. There are drugs approved to treat some of the symptoms of that disease, but no drugs approved to treat the underlying biology of that disease. So we can add a lot of value to patients, families and caregivers, that's key. But we also want to make sure that we're going to succeed as best we can, as best as one can when you're developing novel therapies. So how do we do that?
• 7:48
  Bruce Leuchter: We look at these triangulation exercises. In our case, GRIN, it was human genetics, and we developed conviction around our ability to identify these patients, properly diagnose them, and enrich the patient population that we enroll into the study. And that gives us a higher probability of showing a more impactful clinical effect that will drive even more conviction as we head into pivotal studies, which, of course, is what we're doing right now. So we knew the biology made sense. We knew the mechanistic rationale made sense, and we knew we could leverage pretty significantly human genetics to get us to a better spot. Historically in the treatment of these sorts of diseases, they're often called developmental epileptic encephalopathies, or DEEs, or neurodevelopmental disorders, or NDDs. Typically, you found companies developing symptomatic treatments. So there may be seizures that are a component part of the disease, they're developing an anti-epileptic or anti-seizure medicine to treat those seizures. There may be behavioral symptoms, and doctors may use psychotropic medicines to manage behavioral dysregulation, but they're treating the symptom. And what we thought we could do was organize around rapiprodil, a negative allosteric modulator against the NR2B subunit of the NMDA receptor, do it in patients who we definitively know have hyperactivity at that receptor, given a gain of function mutation, and potentially drive outsized effect in those patients. And we did that in a phase 1b/2A study, a small 15 patient open label data set. But the data were so compelling, so convincing, that despite it being open label and a small number of patients, gave all stakeholders conviction around the potential therapeutic candidate. And so we feel like we've gotten to a mile marker in the course of our life cycle, where we've been able to prove out the thesis, where one can identify an opportunity that exists within another company, do a whole bunch of work to convince ourselves that it's worthy of the commitment that we're aiming to make. License it in, or acquire the asset in develop a special purpose vehicle around it, and that's GRIN Therapeutics, and then deliver on data that gives the broader community conviction around the potential of the drug candidate. And now here we are having done that with GRIN. And the aim for Neurvati would be to reproduce that success across another affiliate co, and, you know, continue to create a flywheel and become a solution for neuroscience therapeutic development, which I'd argue, and I think most would in this space, needs solutions, given the challenges that are inherent in developing drugs in this space. There needs to be ways to get creative around how to take viable technology, resource it appropriately, and deliver it to patients and caregivers. And that's what we're built to do.
• 10:49
  John Simboli: In that early stage, before you knew you had traction, an inkling and the data to support it in the early, early stages. Sometimes a founder, CEO, goes through a process of having to leave something that feels secure in order to take on something that feels hopeful.
• 11:08
  Bruce Leuchter: Without question. And it wasn't a new kind of conversation for me and my family. I've had it a number of times at every mile marker along the way. One experiences, inevitably angst, wondering whether or not the decision is the right decision. Will it yield success in the way that the individual experiences it, but also in the way that his or her family experience it.
• 11:35
  Bruce Leuchter: There's change, inevitable change. And I think change can be disorganizing, destabilizing, anxiety provoking, and it certainly has applied to me and some of the career decisions I've made. But what I've always said along the way to anyone who's asked, is life is not a dress rehearsal. You know, this is the real thing. You've got one chance and go out, learn as much as you can, put yourself by design, in vulnerable positions where there is clearly risk of failure, but do it in a controlled way. Do it in a way where you've developed enough muscle mass so that you can leverage it as you're trying to bob and weave in the new role.
• 12:20
  Bruce Leuchter: And I would say that it's been an incredibly enriching experience to have made the various different pivots that I've made, all of which have come with a certain amount of anxiety. But therein lies the learning. And as I look back and reflect, I couldn't be happier with the amount that I've been able to take on board, synthesize, personalize in my own way, and then apply to achieving success with a firm, with academic colleagues before I was in the financial services side of the business and now with the best in class team. And assuming ,you know, that leadership role has a ton of gravity attached to it. And it isn't just your own personal experience and your testing of your ability to pivot. It's supporting the company, leading the organization, creating the kind of culture, that enables people to want to sacrifice, to want to compete, to want to lock arms, and who believe that one plus one equals three. And that's the beauty of a biotech company, because the expertise are so diversified across the team, lots of advanced degree people, plenty who don't have advanced degrees, who are equally as smart and capable and they have expertise that all contribute to the ultimate success of the organization. And to the earlier comment on data being binary, you progress programs for years and years with countless amounts of investment dollars, and the fate of the program oftentimes hinges on a data point, maybe two, depending on how many pivotal studies you're running. Why would people do that? Why would people take on that binary risk?
• 14:06
  Bruce Leuchter: And the answer isn't, in my mind, because there's economic upside if you succeed. The answer is that in so doing, in all of the blocking and tackling, the sausage making, you are coalescing as a really sharp, capable, intelligent group of people, and the sum is greater than the parts, and it's a living, breathing creature.
• 14:30
  Bruce Leuchter: You have to want a lot of activity and fire drills and things that need to get solved for on a daily basis in order to like this job. But if you want it, you will love the job, because there's all of that and then some. And if you succeed, you've succeeded because you've gotten folks to believe that the team that's being brought to bear on this particular project is a team that can't be beat.
• 14:58
  Bruce Leuchter: And it's not so much being beaten by other people or other companies. It's about winning in coalescing as a group and delivering results that inevitably benefit the communities you're trying to treat. In the event that you do not succeed in getting a drug approved, you have certainly succeeded in giving hope to patients who've participated in the study, patient advocacy organizations who haven't had as much visibility prior to your engagement around their disease, the relationships that you've built, the education that you've provided to all stakeholders.
• 15:29
  Bruce Leuchter: It's beneficial net, net, to be sure, and I think you've got to want that to embrace this, you know this, binary risk that floats above all of our heads.
• 15:45
  John Simboli: When I first started doing the podcast, I was physically going to executives offices and bringing my kit and doing this, and then during the the, you know, the pandemic, of course, I found this format that we're working in today worked.
• 16:01
  John Simboli: And one of the things I found through that discussion was I'd be talking, you know, across a kitchen table, you know, 11 o'clock at night with someone and and they, the family, would pass through the frame, someone from the family passed through.
• 16:14
  John Simboli: And it led to this discussion about what it is that a CEO does at a biopharma company. So here's what I'm trying to get at, an executive at a big pharma company, people probably have a certain idea of what that job is like. It's probably very much a managerial job, because it's a big thing. And then people probably have a rudimentary idea what a scientist does. And they picture being in the lab. What is your day like? When someone says to you, what do you do for a living? How do you try to explain that? How does your day go by?
• 16:46
  Bruce Leuchter: Well, the easiest answer, and I get that question all the time, is I try to develop novel therapies for diseases of the brain and nervous system. I think most people can get that. What they don't necessarily get is how you do it on a day to day basis. And the diversification of experiences that I am able to have, need to have on a daily basis, is just what the doctor ordered. So at any given moment in time, I may be knee deep in an HR related issue, and there are all sorts of considerations that one needs to bring to bear, most of which require some level of mindfulness and self awareness and solution oriented thinking, and that has nothing to do with developing drugs, per se, it's about developing people and managing people, which, as I mentioned in my last comment, is critical to the success of a biotech company. In the next hour after that heavy duty HR meeting, I may find my way into a clinical development meeting talking about clinical trial design, and now I get to put on my neuroscience cap and think about biology. Think about disease states, think about physician behavior. It's gratifying, it's intricate, and it's a big part of what I do. In the hour following that meeting, I may find myself talking to investors who may have macro concerns about the market or the broader neuroscience space, and wonder how our business is accounting for those macro developments. They may be just as much in the weeds on the micro topics, at which point I'm talking about the science that we're progressing and the clinical work that we're doing in a way that is well received or can be well received by an investor who's thinking about deploying capital into an investment. In the hour after that, I could find myself on the line with investment bankers who are wondering whether the IPO markets will reconstitute, and are thinking about the fate of emerging growth biotech companies in the world we currently live in, and all the different three dimensional chess that one needs to play around that as we try to fund the companies that could potentially deliver these treatments to patients, it's the richest of experiences. And for people who do like to bob and weave, which is the terminology I tend to use, there's plenty of it in this role. I think it keeps you sharp. I think you have to care not just about any particular function, but about the broader organization. And you've got to care about your stakeholders. Because as much as you're managing a team of highly capable, gifted people on the operating side, you're managing a team of highly capable, often highly successful people on the board front, and there's a lot of considerations that surround that too. We are in the fortunate position at Neurvati GRIN of having just a tremendous board of directors with people whose experiences range across the industry in all sorts of senior leadership roles, and we benefit from that mind share on a daily basis. But that too requires management So people often say that the CEO role is a lonely role. If I've heard that from one person, I've heard it from 1000. And to some extent they're right about that.
• 20:08
  Bruce Leuchter: There's one person in charge of what I'm in charge of. But I don't see it as an N-of-1 exercise, where one might think about loneliness existing in an N-of-1 world. I see it as an N of infinity world, because in any given moment, whether it's an employee, whether it's the executive leadership team, it's a vendor, aan investor, a banker, a consultant, a stakeholder at the board level, there's constant dialog, constant thought experiments and constant solution oriented thinking. And that doesn't make me feel lonely at all. You have to want to go out and get it and not believe that you don't need it. I think if there's one thing that everyone should learn about this role is that more perspective, more information, you know, more mind expansion equals higher probability of success, and you want to take as much of that on as you possibly can. It requires a healthy ego to do it, but it is definitely beneficial, so I don't experience the sort of classic loneliness that folks talk about. That doesn't mean the job isn't challenging, psychologically. Of course, it is when you're thinking about all the different roles and responsibilities that the CEO plays. But I'm in the fortunate position of working with the best people in the industry, no matter who we're talking about, stakeholders, or the executive leadership team, or or any given person in the company. And for me, that's a big win.
• 21:29
  John Simboli: Your phrase "bob and weave" catches my ear, and I don't want to strain the metaphor, but it certainly brings to mind the image of a boxer and someone who knows how, through their footwork, to approach the moment and when to back off. So to follow that analogy, when you close, when you come in and really engage on something, how do you know when to do that and make whatever decision you have to make as a CEO, versus when to disengage, go back to what you just spoke about, bringing in all the information and try to evaluate it. I imagine it's a never ending, in and out, back and forth. But how does one do that?
• 22:10
  Bruce Leuchter: Well, I think no one should believe that there is ever a perfect decision. And I think if you convinced yourself of that and you're out trying to find it, it may amount to a bit of a wild goose chase. And the bobbing and weaving isn't so much evasion of different opinions, personalities, decisions, etc. It's more nimbleness, you know, light on your feet, figuring out how to move and change with the daily changing environment in which we live as biotech folks. And because there is no perfect decision, it's about triangulating around the best decision. And if you allow perfect to be the enemy of the good, you may never find that decisive moment. You may always be sitting there ambivalating about what it is that's best for the company. But if you take on these different vantage points and you appropriately contextualize them based on the source from which it's coming, I think it gives you enough information to ultimately come to a conclusion that is best for the company, that you believe wholeheartedly is going to yield the most amount of success, and recognize that there are going to be challenges associated with that decision more often than there isn't. And as long as you're prepared to contend with that, you can remain light on your feet. You can continue to bob and weave. It's probably important to think about bob and weave in the way that I do, which isn't so much trying to sidestep problems, you know, trying to bounce around and evade a punch. It's more about trying to get the rhythm of the business, trying to get, trying to understand the people that you're working across from or next to, and incorporate their style into what it is that you need to accomplish. Because it is not monolithic. It is not an N equals 1 role, and it is one that requires onboarding the kinds of perspectives that you perhaps don't have but need to quickly understand to get to the right decision.
• 24:19
  John Simboli: When you were a kid, can you picture thinking I'd like to be this when I grow up? Did the this turn out to be that? What you're doing? Or is this something else?
• 24:29
  Bruce Leuchter: I didn't for a moment see myself pursuing the things that I've pursued, certainly not being the CEO of a biotech company. What I did see was a lot of neurology. And, you know, I had the great fortune of growing up in the home of a brilliant clinician scientist, neurologist, the best doctor I've ever known, really talented physician, and saw the work that he was doing on a daily basis.
• 24:55
  Bruce Leuchter: You know, before the advent of digital technologies and the like. EEG pages strewn across the kitchen table, CSF samples in the freezer getting ready to go back to the office on Monday, go on rounds in the hospital on a Saturday, and saw it firsthand. Thought it was the coolest job in the world and the most privileged relationship that one could develop in the world. For someone who was interested in academics and science, there, in essence, was no other path. So while I can represent to you that becoming a physician was the narrow view I had of my career dating back to as early as I can remember, I can also represent to you that I felt pretty early on that there may be more to it than taking care of patients, as much of a privilege as that is. It felt like the ecosystem was bigger than that, the broader ecosystem of healthcare. I have a hard time articulating it more clearly, because I don't think I understood it any more clearly back in the day, but it did feel like there were other forces at play that were ultimately determining how a patient was treated by their physician, and that got me interested in managed care. I did some work at an HMO back in medical school. I saw pretty early in coming to New York City to train that, you know, you throw a stone, you hit two bankers in New York City and got close to Wall Street, but at a moment in time at which there was an enormous amount of novel therapeutic development. This is the novel anti-epileptics, the novel MS drugs, the pain drugs, the sleep drugs, all the stuff we currently use to treat patients, was happening at that moment in time, and there was just a demand for viewpoints from people who were in physician roles or academic roles. I found my way to that, and that snowballed, and here I am. But again, the governing principle being, I like to learn and I like to challenge myself, and I believe that humility is critical, and I believe that vulnerability is critical to learning, believe it or not, allowing yourself to feel vulnerable. And that I think I've believed for also as long as I can remember, so maybe there is a common thread. But at the end of the day, I was the son of a brilliant physician, and I was beelining straight to medical school.
• 27:21
  John Simboli: who is Neurvati Neurosciences?
• 27:23
  Bruce Leuchter: I tell people, our job is to identify and develop novel therapeutics for diseases of the brain and nervous system. I think most people, whether they're close to biotech or far from it, appreciate that, understand that. We do it in a way that is different than a standard biotech company does, just given our relationship with Blackstone Life Sciences, how they finance the work we do, and how they partner with us on it. Also different in terms of the way in which we innovate, where we look for programs that are going to be externalized from established companies, determine whether or not there's any hazard around that decision to externalize.
• 28:06
  Bruce Leuchter: Often there is not. Often there is just the need to prune portfolios, to rethink strategies in certain therapeutic areas, less of a commentary on an individual program, more of a commentary on an overarching corporate strategy. And we, because of our relationships, both at the Neurvati co level, given everything that each of the senior leaders have done in their careers, and at Blackstone Life Sciences, the network is quite large, and so we find ourselves in bespoke conversations with the world's largest pharma companies and, for that matter, small privately held pharma companies or biotech companies, where there is a need, there is a need for operational expertise, there is a need for alternative financing. And we identify those programs, we diligence them in an incredibly robust way, in a manner that I'm quite proud of, the level of detail, the embrace of the science, the understanding of the clinical development that we need to do, the regulatory path that we'll pursue, the markets that we aim to target, and then we find our way toward establishing a new special purpose vehicle, or affiliate co and then progressing it into late and through late stage development to approval. So again, the easiest way to say it is we develop neuroscience therapeutics, and we do it in a way that leverages the operational capabilities that we have and the financial backing that we have from our partner,
• 29:27
  John Simboli: Let's say that at an investor conference, and you begin to give the description of who you are as a company, as you've been giving it to me, and you get that moment when someone wants to put your company, into a particular category. And sometimes it's the right one, sometimes it's wrong one. It's been my experience that often the CEO's job is to help to educate at that point so that you know they don't get stuck in the wrong spot. So are there wrong spots that Neurvati would get placed into? And if there are, what are they? What is that pattern? And then how do you help get out of that pattern?
• 30:04
  John Simboli: think
• 30:05
  Bruce Leuchter: I think our model requires explanation.
• 30:09
  Bruce Leuchter: Because as much as we develop mid to late stage therapeutics, there are unique features that I think people need to understand, for them to fully appreciate what our mandate is and how we do it. We certainly want people focused on the affiliate co work that we do, particularly where we are right now with GRIN Therapeutics, heading into a phase three study, there's all kinds of motivation around educating the stakeholder, community, investors, strategics and others, on how promising this development stage therapeutic is and how focused we are on progressing the ball down the field and gaining approval, ultimately, and delivering it to patients. So we want the spotlight on the affiliate co. But we also want people to understand that away from the affiliate co are all of these capabilities that can be leveraged against a very broad swath of neuroscience. I think typically when people think about biotech companies, they think about those companies pursuing perhaps one or two verticals within a given therapeutic area. So if you're developing a drug for psychiatric indications, you likely organize around additional psychiatric indications. If you're developing a drug against a neuroinflammatory disease, you're organizing around broader neuroinflammatory diseases or adjacent indications. And what's different about us is that we are not restricted to a given number of verticals. It's really important that people understand that, because what we want folks to appreciate is that we have the ability to look across the waterfront of neuroscience, and even though we are sitting here today talking about neurodevelopmental disease for GRIN Therapeutics and wanting people to understand what it is that we do around radiprodil in these diseases, we also want people to realize that if there are opportunities away from neurodevelopmental disease or away from orphan neurology that are focused on sleep/wake as an example, or focused on pain, or, for that matter, neuro oncology, glioblastomas, or malignant brain tumors, that we have an opportunity because of our sponsor, to go think about those diseases, apply the same amount of rigor, deliver the same kind of best-in-class work product around its viability, and if we get there, pursue it, even though one would argue that neuro oncology is very different than neurodevelopmental disease.
• 32:30
  Bruce Leuchter: And we think that's okay, because, in our view, what the space really needs is champions for viable drug candidates, viable therapeutic candidates.
• 32:44
  Bruce Leuchter: It needs to have people who are willing to roll up sleeves, get into the weeds, make careful decisions around what's best for any given program, and not be restricted to a given vertical within neuroscience. Because at the end of the day, we want to take clinical stage product candidates, properly resource them, deliver the ultimate data point, gain approval, and find our way to patients through whatever mechanism. Could be us commercializing the drug. Could be us putting it in the hands of a vertically integrated organization that is already commercializing against the same call point, against the same position. And what we've noted, this is a very generic comment to all of our peers across the biopharma landscape., but what we've noted is that it's not always true that you can work on everything that you want to work on. And in some cases, despite a product candidate being perfectly viable, fundamentally, there are reasons for companies to externalize or terminate their own resource allocation against that program. And because we're not restricted to any of these given verticals, per se, we can take that robust data set and we can create value around it. We can progress the ball down the field in a way that one may not have otherwise been able to do. And that's a privilege, and so we want people to know that. That is, if I had to argue that there's one distinct difference between us and others, is that our common denominator is data, is robustness of clinical data sets, and what that is allowing us to believe about downstream success. It is not restricted to a view on a certain vertical of neuroscience.
• 34:25
  John Simboli: It would seem that that would take a sophisticated partner to absorb that and understand that. On the other hand, it would seem it could be breathtaking in the right conversation. Is that a fair statement?
• 34:42
  Bruce Leuchter: It's a fair statement. I think the ambition level is high when one tries to tackle, you know, an entire therapeutic area the size of neuroscience. And what we've done as an organization is remain relatively lean, certainly relative to other companies heading into Phase 3 studies, and we've done that for a reason. We're certainly fit for purpose. We've got all the capabilities and muscle that we need to progress our programs, but we know that the next opportunity we work on may require slightly different expertise, that may require a different fit for purpose view on who we hire and who organizes around that next project. And they're going to be plenty of people who organize around all projects that we take on, but there may be more bespoke expertise and capabilities that are mandated, required in order for us to succeed in the next affiliate co, we've got the opportunity to bring those folks in. So we don't believe, as I said earlier in the conversation, no one's good at everything. Expertise are called expertise for a reason. And as we organize around opportunities, we look for the best expertise that will give us the highest probability of succeeding around that affiliate co. And that's what our model has enabled.
• 35:54
  John Simboli: If GRIN succeeds the way you hope it will, do you allow yourself, at this point to picture how transformational your therapeutic might be, and what is the need? What's not being served? Just how could you change the equation?
• 36:11
  Bruce Leuchter: Important question. We believe that we have an opportunity to materially impact the lives of patients, caregivers and families in a way that hasn't yet been done. So it is very true and important to note that companies have had significant success around rare pediatric epilepsies and neurodevelopmental diseases, particularly over the last 10 years, where I would argue human genetics have enabled more definitive diagnosis awareness, visibility of these diseases has increased, and the tide in general has been rising. But the success to this point has been largely around treating symptoms of disease, not treating the underlying disease biology, in this particular part of the of the neuroscience universe, where we're talking about neurodevelopmental diseases and developmental epileptic encephalopathies. Some of the therapeutic modalities that have come to the forefront over the last 5-10, years, gene therapies, oligonucleotide therapies, genetic medicines, are increasingly more often putting this on the radar screen of physicians, KOLs and companies, investors, for that matter, that you can actually take a rifle shot, as opposed to a buckshot, at these diseases.
• 37:26
  Bruce Leuchter: But as I do think forward to delivering Phase 3 data in GRIN related NDD, and engaging with regulators around potential approval and the impact that it may have on patients, it's not just the impact that it can have on GRIN and its families. It's the impact that it can have for diseases that are also genetically defined. If we succeed in demonstrating that one can pursue underlying disease biology associated with these diseases, it gives hope, encouragement, motivation, energy, to doing the same thing across a number of different genetically defined diseases for which there is no therapeutic candidate in development, and for which there is no disease specific treatment, there is only an ability to treat symptoms. And part of what we're trying to talk to folks about, irrespective of constituency, is that creating disease specific treatments, creating treatments that go after the underlying disease process and target that biology, has to be the way in which we think about therapeutic development going forward, because it's got the greatest chance at delivering the most pronounced effect size and helping these patients maximally. I think if we spend our time, all of our time, continuing to pursue symptomatic treatments, we leave a lot on the table that these patients suffer from. And while we can see something like seizure, now you can actually see a patient have an epileptic seizure, what is harder to see is the impact of the non seizure symptoms on the patients, the families and the caregivers and the clinicians who treat them. By going after the broader disease state in the way that we are with radiprodil in GRIN NDD, we're giving these patients and all of the associated constituencies an opportunity to target the underlying disease biology. And that, I hope, is catalytic to additional work that can be done across additional diseases, where the bona fides are there. We've shown it can be done, and we get more momentum to treat these kids. When I was training in neurology, and I was looking, I was rotating through pediatric neurology clinics, cynically, very cynically, you found people saying, particularly those who weren't going into neurology, that neurology was a "diagnose and adios" subspecialty. You can make the diagnosis. It can be a very sophisticated diagnostic workup, and it can yield a lot of information. And then, in essence, you bid adieu, adios to the patient., Because there just wasn't anything to treat them with, right? And we have most definitely made progress over the last 30 years in that regard. But I'd argue there's been an acceleration of that process over the course of the last five to 10 years where these sorts of disease specific treatments are now possible, such that no one contemplating a career in neurology has to ever hear "diagnose and adios" again, because it is not the way I think about neurology, and it's not the way we need to think about neurology today, given all the technological advancements.
• 40:32
  John Simboli: Bruce, what's a good partner for Neurvati?
• 40:34
  Bruce Leuchter: It's a long list, John. There is no favored nation in our business. We are focused on the fundamentals associated with developing neurotherapeutics. That can happen in a number of different contexts. It is certainly true that large cap biopharmaceutical companies is where we spend a lot of time. That's where most of the portfolio reorganization and some of the strategic shifting occurs that enables opportunities for externalizing viable technologies. But it's also true that if you swung the pendulum to the other side, you'd find privately held or micro cap, small cap biopharma companies that may be challenged right now by the current market conditions, may not be able to finance all the work that they'd like to do, and may be under pressure to find solutions.
• 41:23
  Bruce Leuchter: Their technologies may be equally as viable as the technologies of a multinational, large cap biopharma company. And then, of course, there's everyone in between. And everyone in between doesn't just include companies. There are investors in the world who've chosen to organize around neuroscience therapeutics and are looking for ways in which to collaborate, looking for ways to progress. There are programs that they've already gotten behind, but now need some help with. So we see our audience as a very broad audience. I would argue that you might include key opinion leaders and principal investigators in that audience.
• 42:03
  Bruce Leuchter: We find ourselves in discussions with the world's leading scientists on some of the recent discoveries that they've made that can be mapped on to a clinical thesis surrounding a certain drug candidate. And that kind of innovation may not happen in a wet lab, for us, but certainly can leverage the work that does happen in wet labs, and for sure, manage, leverage rather, the work that these top tier thought leaders are willing to share with us. So we don't have a view that our model is appropriate for a small carve out of the industry. We have the view that neuroscience is critically important. It's important to our industry, but moreover, it's important to the world in which we live, where the unmet need is sky high, the viable technologies, while increasing in number, are still not enough. We see the universe is big, and we see it with a lot of opportunity, and we think we've got the right team members, the right supporters, the right advisors to help us succeed in the long term.
• 43:01
  John Simboli: Thanks for speaking with me today, Bruce.
• 43:04
  Bruce Leuchter: Thank you, John, it was a pleasure, and I enjoyed the conversation. Lots of important topics to discuss, and I'm glad we hit on a number of them.