September 29, 2025 • 46 mins
Bruce Leuchter, CEO of Neurvati Neurosciences, shares his insights about leadership in biopharma and how Neurvati is working to advance drugs with the potential to improve the health and lives of people living with neurological and psychiatric disorders.
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John Simboli (00:00):
Bruce, welcome to BioBoss.
Bruce Leuchter (00:02):
Thanks, John, pleasure to be here.
John Simboli (00:03):
Bruce, what led you to your role as cofounder
and CEO of NeurvatiNeurosciences?
Bruce Leuchter (00:09):
It draws on a number of different experiences
that I've had over the course ofmy career. And, you know, I grew
up in the home of a brilliantclinician-scientist neurologist,
found my way into neurologyresidency, then did some
training in psychiatry, becauseI felt like I was getting half
the story. So doing bothneurology and psychiatry
broadened my horizons aroundthinking through issues related
(00:32):
to the brain and nervous system.
And from there, I believed thatunderstanding industry, and as
part of that, financial servicesin healthcare and biotech, would
create another dimension to thework that I had done to date,
but use the scientific andclinical perspective, and
frankly, my love of those twodimensions of my life, the
(00:55):
scientific training and clinicalexperience to inform how I
performed my role in thefinancial services sector. And
it was always a third leg of thestool to be able to leverage all
of that in actually operating aneuroscience-focused biotech
company. I think there's nogreater privilege beyond,
perhaps, taking care of patientsthat one can have than
(01:18):
developing a novel therapy for adisease with high unmet medical
need. And that is our mandate atNeurvati, and we get to do it
with best-in-class sponsors,financial partners who help us
along the way. And that'sultimately what led to me
sitting in this seat, which, aswe'll talk about, I'm sure later
on in the discussion, has someunique features to it that draw,
(01:40):
in particular, on the number ofdifferent professional
experiences I've had over time
John Simboli (01:46):
When you were thinking about that, how you
would apply your background andyour interest in, and seeing how
it could turn into, perhaps, atherapy someday, you must have
looked at a lot of differentoptions and a lot of different
possibilities. How did you landon the one that enabled you to
become the co-founder?
Bruce Leuchter (02:06):
Well, I think we in biotech often find ourselves
looking across the landscape ofopportunities. And in many
cases, particularly in theventure world, you find early
stage science, perhaps comingout of a top tier academic
institution, or pre-clinicalassets, molecules that are in
(02:27):
development, pre-clinically thathaven't yet found their way to
the clinic. And then you workyour way downstream and find
clinical data sets around whichyou can organize for
opportunities that exist in themarket. And for our investors,
Blackstone Life Sciences, theclinical data is really
important, and it's importantbecause we focus our efforts on
mid and late stage drugdevelopment, where often
(02:50):
companies find themselves invarious different circumstances
that preclude progressingprograms internally and require
externalizing those programs,putting them in the hands of
entrepreneurs who, in ourcircumstance, have the necessary
amount of capital to finance,they've been in late stage
development. So for us, whilethere is a ton of raw material
(03:14):
out there, early stagetechnologies that hold a
tremendous amount of promise,our mandate is one where we need
to look at mid and late stagedevelopment, and there are some
unique challenges associatedwith that. Neuroscience is a
space that has a prettysignificant capital requirement
to develop drugs throughapproval. Timelines can
sometimes be more prolonged thanother therapeutic areas, and
(03:36):
risk is quite high. And it's notwithout understanding all of
those things that people makedecisions around neuroscience,
product candidates, and for us,focusing on that later stage of
development where we canorganize around data, clinical
data and pre-clinical data thatgive us conviction, is critical
to getting a new affiliate coover the finish line and in our
(03:58):
first affiliate co, GRINTherapeutics, that fact pattern
existed. We had a molecule thathad a significant amount of
clinical data, had a whole lotfor us to look at in terms of
safety, tolerability, dosing,protocol, PK, and even data in
certain neuroscienceindications. And when we coupled
that with GRIN relatedneurodevelopmental disorder and
(04:19):
knew that we could use humangenetics to identify the most
appropriate patient to enroll inour study, and combine that with
the dossier that we had aroundthis program, it made a whole
lot of sense to push off on thisparticular opportunity, and
we've been at it now for fouryears.
John Simboli (04:35):
Does your work put you at the head of GRIN and
Neurvati?
Bruce Leuchter (04:40):
So Neurvati Neurosciences is an operating
company, a development companythat is owned by Blackstone Life
Sciences, and it was created towork on neuroscience
therapeutics across thewaterfront, which means that
we're not restricted to aparticular vertical in
neuroscience. So as an example,right now, GRIN Therapeutics is
(05:02):
focused on neurodevelopmentaldisease, but we look at
opportunities that are in theclinic with critical mass data
that could be in the neurooncology space, could be in the
neurovascular space,neuromuscular space,
neuroinflammatory disease space,neuropsychiatry, pain, sleep,
wake. All of these verticals forus are options, and the lowest
(05:23):
common denominator is whether ornot there's enough data to
support a highly convicted viewaround success in mid and late
stage development and regulatorydiscussions. So what Neurvati
does is operate those affiliateco's, and that's where the
people sit, the human capital,but all of the action, or
activity, if you will, exists atthe affiliate co level. The
(05:45):
Neurvati team drops down intothat affiliate co and executes.
So all of the functions thatyou'd ordinarily expect to see
within a biotech companycertainly exist. They exist at
the Neurvati co level, and thenthe day-to-day execution occurs
in the affiliate co. And that'swhere the asset sits, that's
where the capital flows when weraise capital. That's where the
(06:08):
governance sits, where theincentive structure sits. And it
allows us, as Neurvati, tocontinue to progress this sort
of work across a number ofdifferent projects going
forward. But the project that wehave in hand right now, that
we're solely focused on is GRIN,GRIN related neurodevelopmental
disorder, and the development ofradiprodil to treat these kids
(06:31):
with a really difficult andhighly morbid disease process.
When we look at opportunities,we are focused on human
genetics. We want to haveclarity around the patient
population that suffers from thedisease, how we can identify
those patients, definitivelydiagnose those patients, and
(06:52):
deliver precision therapeuticsto those patients. People define
precision therapeutics invarious different ways, with
various different therapeuticmodalities. But the bottom line
is that we're aiming to usehuman genetics, biomarkers of
all sorts, whether they are fromthe cerebral spinal fluid,
whether they are imagingbiomarkers, electrophysiologic
biomarkers, to try totriangulate around the patient
(07:14):
population that is best suitedto enroll in a study and to
potentially benefit from anexperimental therapy, should it
get approved. And that's exactlywhat we did with GRIN. We said
there's a genetically defineddisease in GRIN related
neurodevelopmental disorder.
There are no drugs approved totreat that disease. There are
drugs approved to treat some ofthe symptoms of that disease,
but no drugs approved to treatthe underlying biology of that
(07:34):
disease. So we can add a lot ofvalue to patients, families and
caregivers, that's key. But wealso want to make sure that
we're going to succeed as bestwe can, as best as one can when
you're developing noveltherapies. So how do we do that?
We look at these triangulationexercises. In our case, GRIN, it
was human genetics, and wedeveloped conviction around our
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ability to identify thesepatients, properly diagnose
them, and enrich the patientpopulation that we enroll into
the study. And that gives us ahigher probability of showing a
more impactful clinical effectthat will drive even more
conviction as we head intopivotal studies, which, of
course, is what we're doingright now. So we knew the
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biology made sense. We knew themechanistic rationale made
sense, and we knew we couldleverage pretty significantly
human genetics to get us to abetter spot. Historically in the
treatment of these sorts ofdiseases, they're often called
developmental epilepticencephalopathies, or DEEs, or
neurodevelopmental disorders, orNDDs. Typically, you found
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companies developing symptomatictreatments. So there may be
seizures that are a componentpart of the disease, they're
developing an anti-epileptic oranti-seizure medicine to treat
those seizures. There may bebehavioral symptoms, and doctors
may use psychotropic medicinesto manage behavioral
dysregulation, but they'retreating the symptom. And what
(09:00):
we thought we could do wasorganize around rapiprodil, a
negative allosteric modulatoragainst the NR2B subunit of the
NMDA receptor, do it in patientswho we definitively know have
hyperactivity at that receptor,given a gain of function
mutation, and potentially driveoutsized effect in those
patients. And we did that in aphase 1b/2A study, a small 15
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patient open label data set. Butthe data were so compelling, so
convincing, that despite itbeing open label and a small
number of patients, gave allstakeholders conviction around
the potential therapeuticcandidate. And so we feel like
we've gotten to a mile marker inthe course of our life cycle,
where we've been able to proveout the thesis, where one can
(09:46):
identify an opportunity thatexists within another company,
do a whole bunch of work toconvince ourselves that it's
worthy of the commitment thatwe're aiming to make. License it
in, or acquire the asset indevelop a special purpose
vehicle around it, and that'sGRIN Therapeutics, and then
deliver on data that gives thebroader community conviction
(10:08):
around the potential of the drugcandidate. And now here we are
having done that with GRIN. Andthe aim for Neurvati would be to
reproduce that success acrossanother affiliate co, and, you
know, continue to create aflywheel and become a solution
for neuroscience therapeuticdevelopment, which I'd argue,
and I think most would in thisspace, needs solutions, given
(10:31):
the challenges that are inherentin developing drugs in this
space. There needs to be ways toget creative around how to take
viable technology, resource itappropriately, and deliver it to
patients and caregivers. Andthat's what we're built to do.
John Simboli (10:49):
In that early stage, before you knew you had
traction, an inkling and thedata to support it in the early,
early stages. Sometimes afounder, CEO, goes through a
process of having to leavesomething that feels secure in
order to take on something thatfeels hopeful.
Bruce Leuchter (11:08):
Without question. And it wasn't a new
kind of conversation for me andmy family. I've had it a number
of times at every mile markeralong the way. One experiences,
inevitably angst, wonderingwhether or not the decision is
the right decision. Will ityield success in the way that
(11:30):
the individual experiences it,but also in the way that his or
her family experience it.
There's change, inevitablechange. And I think change can
be disorganizing, destabilizing,anxiety provoking, and it
certainly has applied to me andsome of the career decisions
I've made. But what I've alwayssaid along the way to anyone
who's asked, is life is not adress rehearsal. You know, this
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is the real thing. You've gotone chance and go out, learn as
much as you can, put yourself bydesign, in vulnerable positions
where there is clearly risk offailure, but do it in a
controlled way. Do it in a waywhere you've developed enough
muscle mass so that you canleverage it as you're trying to
(12:16):
bob and weave in the new role.
And I would say that it's beenan incredibly enriching
experience to have made thevarious different pivots that
I've made, all of which havecome with a certain amount of
anxiety. But therein lies thelearning. And as I look back and
reflect, I couldn't be happierwith the amount that I've been
(12:39):
able to take on board,synthesize, personalize in my
own way, and then apply toachieving success with a firm,
with academic colleagues beforeI was in the financial services
side of the business and nowwith the best in class team. And
assuming ,you know, thatleadership role has a ton of
gravity attached to it. And itisn't just your own personal
(13:03):
experience and your testing ofyour ability to pivot. It's
supporting the company, leadingthe organization, creating the
kind of culture, that enablespeople to want to sacrifice, to
want to compete, to want to lockarms, and who believe that one
plus one equals three. Andthat's the beauty of a biotech
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company, because the expertiseare so diversified across the
team, lots of advanced degreepeople, plenty who don't have
advanced degrees, who areequally as smart and capable and
they have expertise that allcontribute to the ultimate
success of the organization. Andto the earlier comment on data
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being binary, you progressprograms for years and years
with countless amounts ofinvestment dollars, and the fate
of the program oftentimes hingeson a data point, maybe two,
depending on how many pivotalstudies you're running. Why
would people do that? Why wouldpeople take on that binary risk?
(14:06):
And the answer isn't, in mymind, because there's economic
upside if you succeed. Theanswer is that in so doing, in
all of the blocking andtackling, the sausage making,
you are coalescing as a reallysharp, capable, intelligent
group of people, and the sum isgreater than the parts, and it's
(14:30):
a living, breathing creature.
You have to want a lot ofactivity and fire drills and
things that need to get solvedfor on a daily basis in order to
like this job. But if you wantit, you will love the job,
because there's all of that andthen some. And if you succeed,
you've succeeded because you'vegotten folks to believe that the
team that's being brought tobear on this particular project
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is a team that can't be beat.
And it's not so much beingbeaten by other people or other
companies. It's about winning incoalescing as a group and
delivering results thatinevitably benefit the
communities you're trying totreat. In the event that you do
not succeed in getting a drugapproved, you have certainly
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succeeded in giving hope topatients who've participated in
the study, patient advocacyorganizations who haven't had as
much visibility prior to yourengagement around their disease,
the relationships that you'vebuilt, the education that you've
provided to all stakeholders.
It's beneficial net, net, to besure, and I think you've got to
want that to embrace this, youknow this, binary risk that
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floats above all of our heads.
John Simboli (15:45):
When I first started doing the podcast, I was
physically going to executivesoffices and bringing my kit and
doing this, and then during thethe, you know, the pandemic, of
course, I found this format thatwe're working in today worked.
And one of the things I foundthrough that discussion was I'd
be talking, you know, across akitchen table, you know, 11
(16:08):
o'clock at night with someoneand and they, the family, would
pass through the frame, someonefrom the family passed through.
And it led to this discussionabout what it is that a CEO does
at a biopharma company. Sohere's what I'm trying to get
at, an executive at a big pharmacompany, people probably have a
certain idea of what that job islike. It's probably very much a
(16:28):
managerial job, because it's abig thing. And then people
probably have a rudimentary ideawhat a scientist does. And they
picture being in the lab. Whatis your day like? When someone
says to you, what do you do fora living? How do you try to
explain that? How does your daygo by?
Bruce Leuchter (16:46):
Well, the easiest answer, and I get that
question all the time, is I tryto develop novel therapies for
diseases of the brain andnervous system. I think most
people can get that. What theydon't necessarily get is how you
do it on a day to day basis. Andthe diversification of
experiences that I am able tohave, need to have on a daily
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basis, is just what the doctorordered. So at any given moment
in time, I may be knee deep inan HR related issue, and there
are all sorts of considerationsthat one needs to bring to bear,
most of which require some levelof mindfulness and self
awareness and solution orientedthinking, and that has nothing
to do with developing drugs, perse, it's about developing people
(17:32):
and managing people, which, as Imentioned in my last comment, is
critical to the success of abiotech company. In the next
hour after that heavy duty HRmeeting, I may find my way into
a clinical development meetingtalking about clinical trial
design, and now I get to put onmy neuroscience cap and think
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about biology. Think aboutdisease states, think about
physician behavior. It'sgratifying, it's intricate, and
it's a big part of what I do. Inthe hour following that meeting,
I may find myself talking toinvestors who may have macro
concerns about the market or thebroader neuroscience space, and
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wonder how our business isaccounting for those macro
developments. They may be justas much in the weeds on the
micro topics, at which point I'mtalking about the science that
we're progressing and theclinical work that we're doing
in a way that is well receivedor can be well received by an
investor who's thinking aboutdeploying capital into an
(18:38):
investment. In the hour afterthat, I could find myself on the
line with investment bankers whoare wondering whether the IPO
markets will reconstitute, andare thinking about the fate of
emerging growth biotechcompanies in the world we
currently live in, and all thedifferent three dimensional
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chess that one needs to playaround that as we try to fund
the companies that couldpotentially deliver these
treatments to patients, it's therichest of experiences. And for
people who do like to bob andweave, which is the terminology
I tend to use, there's plenty ofit in this role. I think it
keeps you sharp. I think youhave to care not just about any
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particular function, but aboutthe broader organization. And
you've got to care about yourstakeholders. Because as much as
you're managing a team of highlycapable, gifted people on the
operating side, you're managinga team of highly capable, often
highly successful people on theboard front, and there's a lot
of considerations that surroundthat too. We are in the
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fortunate position at NeurvatiGRIN of having just a tremendous
board of directors with peoplewhose experiences range across
the industry in all sorts ofsenior leadership roles, and we
benefit from that mind share ona daily basis. But that too
requires management So peopleoften say that the CEO role is a
lonely role. If I've heard thatfrom one person, I've heard it
(20:05):
from 1000. And to some extentthey're right about that.
There's one person in charge ofwhat I'm in charge of. But I
don't see it as an N-of-1exercise, where one might think
about loneliness existing in anN-of-1 world. I see it as an N
of infinity world, because inany given moment, whether it's
an employee, whether it's theexecutive leadership team, it's
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a vendor, aan investor, abanker, a consultant, a
stakeholder at the board level,there's constant dialog,
constant thought experiments andconstant solution oriented
thinking. And that doesn't makeme feel lonely at all. You have
to want to go out and get it andnot believe that you don't need
it. I think if there's one thingthat everyone should learn about
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this role is that moreperspective, more information,
you know, more mind expansionequals higher probability of
success, and you want to take asmuch of that on as you possibly
can. It requires a healthy egoto do it, but it is definitely
beneficial, so I don'texperience the sort of classic
loneliness that folks talkabout. That doesn't mean the job
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isn't challenging,psychologically. Of course, it
is when you're thinking aboutall the different roles and
responsibilities that the CEOplays. But I'm in the fortunate
position of working with thebest people in the industry, no
matter who we're talking about,stakeholders, or the executive
leadership team, or or any givenperson in the company. And for
me, that's a big win.
John Simboli (21:29):
Your phrase "bob and weave" catches my ear, and I
don't want to strain themetaphor, but it certainly
brings to mind the image of aboxer and someone who knows how,
through their footwork, toapproach the moment and when to
back off. So to follow thatanalogy, when you close, when
you come in and really engage onsomething, how do you know when
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to do that and make whateverdecision you have to make as a
CEO, versus when to disengage,go back to what you just spoke
about, bringing in all theinformation and try to evaluate
it. I imagine it's a neverending, in and out, back and
forth. But how does one do that?
Bruce Leuchter (22:10):
Well, I think no one should believe that there is
ever a perfect decision. And Ithink if you convinced yourself
of that and you're out trying tofind it, it may amount to a bit
of a wild goose chase. And thebobbing and weaving isn't so
much evasion of differentopinions, personalities,
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decisions, etc. It's morenimbleness, you know, light on
your feet, figuring out how tomove and change with the daily
changing environment in which welive as biotech folks. And
because there is no perfectdecision, it's about
triangulating around the bestdecision. And if you allow
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perfect to be the enemy of thegood, you may never find that
decisive moment. You may alwaysbe sitting there ambivalating
about what it is that's best forthe company. But if you take on
these different vantage pointsand you appropriately
contextualize them based on thesource from which it's coming, I
think it gives you enoughinformation to ultimately come
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to a conclusion that is best forthe company, that you believe
wholeheartedly is going to yieldthe most amount of success, and
recognize that there are goingto be challenges associated with
that decision more often thanthere isn't. And as long as
you're prepared to contend withthat, you can remain light on
your feet. You can continue tobob and weave. It's probably
important to think about bob andweave in the way that I do,
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which isn't so much trying tosidestep problems, you know,
trying to bounce around andevade a punch. It's more about
trying to get the rhythm of thebusiness, trying to get, trying
to understand the people thatyou're working across from or
next to, and incorporate theirstyle into what it is that you
need to accomplish. Because itis not monolithic. It is not an
(24:05):
N equals 1 role, and it is onethat requires onboarding the
kinds of perspectives that youperhaps don't have but need to
quickly understand to get to theright decision.
John Simboli (24:19):
When you were a kid, can you picture thinking
I'd like to be this when I growup? Did the this turn out to be
that? What you're doing? Or isthis something else?
Bruce Leuchter (24:29):
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 seewas a lot of neurology. And, you
know, I had the great fortune ofgrowing up in the home of a
brilliant clinician scientist,neurologist, the best doctor
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I've ever known, really talentedphysician, and saw the work that
he was doing on a daily basis.
You know, before the advent ofdigital technologies and the
like. EEG pages strewn acrossthe kitchen table, CSF samples
in the freezer getting ready togo back to the office on Monday,
go on rounds in the hospital ona Saturday, and saw it
firsthand. Thought it was thecoolest job in the world and the
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most privileged relationshipthat one could develop in the
world. For someone who wasinterested in academics and
science, there, in essence, wasno other path. So while I can
represent to you that becoming aphysician was the narrow view I
had of my career dating back toas early as I can remember, I
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can also represent to you that Ifelt pretty early on that there
may be more to it than takingcare of patients, as much of a
privilege as that is. It feltlike the ecosystem was bigger
than that, the broader ecosystemof healthcare. I have a hard
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time articulating it moreclearly, because I don't think I
understood it any more clearlyback in the day, but it did feel
like there were other forces atplay that were ultimately
determining how a patient wastreated by their physician, and
that got me interested inmanaged care. I did some work at
an HMO back in medical school. Isaw pretty early in coming to
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New York City to train that, youknow, you throw a stone, you hit
two bankers in New York City andgot close to Wall Street, but at
a moment in time at which therewas an enormous amount of novel
therapeutic development. This isthe novel anti-epileptics, the
novel MS drugs, the pain drugs,the sleep drugs, all the stuff
we currently use to treatpatients, was happening at that
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moment in time, and there wasjust a demand for viewpoints
from people who were inphysician roles or academic
roles. I found my way to that,and that snowballed, and here I
am. But again, the governingprinciple being, I like to learn
and I like to challenge myself,and I believe that humility is
critical, and I believe thatvulnerability is critical to
(27:01):
learning, believe it or not,allowing yourself to feel
vulnerable. And that I thinkI've believed for also as long
as I can remember, so maybethere is a common thread. But at
the end of the day, I was theson of a brilliant physician,
and I was beelining straight tomedical school.
John Simboli (27:21):
who is Neurvati Neurosciences?
Bruce Leuchter (27:23):
I tell people, our job is to identify and
develop novel therapeutics fordiseases of the brain and
nervous system. I think mostpeople, whether they're close to
biotech or far from it,appreciate that, understand
that. We do it in a way that isdifferent than a standard
(27:44):
biotech company does, just givenour relationship with Blackstone
Life Sciences, how they financethe work we do, and how they
partner with us on it. Alsodifferent in terms of the way in
which we innovate, where we lookfor programs that are going to
be externalized from establishedcompanies, determine whether or
not there's any hazard aroundthat decision to externalize.
(28:06):
Often there is not. Often thereis just the need to prune
portfolios, to rethinkstrategies in certain
therapeutic areas, less of acommentary on an individual
program, more of a commentary onan overarching corporate
strategy. And we, because of ourrelationships, both at the
Neurvati co level, giveneverything that each of the
(28:27):
senior leaders have done intheir careers, and at Blackstone
Life Sciences, the network isquite large, and so we find
ourselves in bespokeconversations with the world's
largest pharma companies and,for that matter, small privately
held pharma companies or biotechcompanies, where there is a
need, there is a need foroperational expertise, there is
a need for alternativefinancing. And we identify those
(28:48):
programs, we diligence them inan incredibly robust way, in a
manner that I'm quite proud of,the level of detail, the embrace
of the science, theunderstanding of the clinical
development that we need to do,the regulatory path that we'll
pursue, the markets that we aimto target, and then we find our
way toward establishing a newspecial purpose vehicle, or
(29:10):
affiliate co and thenprogressing it into late and
through late stage developmentto approval. So again, the
easiest way to say it is wedevelop neuroscience
therapeutics, and we do it in away that leverages the
operational capabilities that wehave and the financial backing
that we have from our partner,
John Simboli (29:27):
Let's say that at an investor conference, and you
begin to give the description ofwho you are as a company, as
you've been giving it to me, andyou get that moment when someone
wants to put your company, intoa particular category. And
sometimes it's the right one,sometimes it's wrong one. It's
been my experience that oftenthe CEO's job is to help to
(29:48):
educate at that point so thatyou know they don't get stuck in
the wrong spot. So are therewrong spots that Neurvati would
get placed into? And if thereare, what are they? What is that
pattern? And then how do youhelp get out of that pattern?
think
Bruce Leuchter (30:05):
I think our model requires explanation.
Because as much as we developmid to late stage therapeutics,
there are unique features that Ithink people need to understand,
for them to fully appreciatewhat our mandate is and how we
do it. We certainly want peoplefocused on the affiliate co work
that we do, particularly wherewe are right now with GRIN
(30:27):
Therapeutics, heading into aphase three study, there's all
kinds of motivation aroundeducating the stakeholder,
community, investors, strategicsand others, on how promising
this development stagetherapeutic is and how focused
we are on progressing the balldown the field and gaining
approval, ultimately, anddelivering it to patients. So we
want the spotlight on theaffiliate co. But we also want
(30:50):
people to understand that awayfrom the affiliate co are all of
these capabilities that can beleveraged against a very broad
swath of neuroscience. I thinktypically when people think
about biotech companies, theythink about those companies
pursuing perhaps one or twoverticals within a given
(31:11):
therapeutic area. So if you'redeveloping a drug for
psychiatric indications, youlikely organize around
additional psychiatricindications. If you're
developing a drug against aneuroinflammatory disease,
you're organizing around broaderneuroinflammatory diseases or
adjacent indications. And what'sdifferent about us is that we
are not restricted to a givennumber of verticals. It's really
(31:32):
important that people understandthat, because what we want folks
to appreciate is that we havethe ability to look across the
waterfront of neuroscience, andeven though we are sitting here
today talking aboutneurodevelopmental disease for
GRIN Therapeutics and wantingpeople to understand what it is
that we do around radiprodil inthese diseases, we also want
(31:53):
people to realize that if thereare opportunities away from
neurodevelopmental disease oraway from orphan neurology that
are focused on sleep/wake as anexample, or focused on pain, or,
for that matter, neuro oncology,glioblastomas, or malignant
brain tumors, that we have anopportunity because of our
(32:15):
sponsor, to go think about thosediseases, apply the same amount
of rigor, deliver the same kindof best-in-class work product
around its viability, and if weget there, pursue it, even
though one would argue thatneuro oncology is very different
than neurodevelopmental disease.
And we think that's okay,because, in our view, what the
space really needs is championsfor viable drug candidates,
(32:39):
viable therapeutic candidates.
It needs to have people who arewilling to roll up sleeves, get
into the weeds, make carefuldecisions around what's best for
any given program, and not berestricted to a given vertical
within neuroscience. Because atthe end of the day, we want to
(32:59):
take clinical stage productcandidates, properly resource
them, deliver the ultimate datapoint, gain approval, and find
our way to patients throughwhatever mechanism. Could be us
commercializing the drug. Couldbe us putting it in the hands of
a vertically integratedorganization that is already
commercializing against the samecall point, against the same
(33:22):
position. And what we've noted,this is a very generic comment
to all of our peers across thebiopharma landscape., but what
we've noted is that it's notalways true that you can work on
everything that you want to workon. And in some cases, despite a
product candidate beingperfectly viable, fundamentally,
there are reasons for companiesto externalize or terminate
(33:45):
their own resource allocationagainst that program. And
because we're not restricted toany of these given verticals,
per se, we can take that robustdata set and we can create value
around it. We can progress theball down the field in a way
that one may not have otherwisebeen able to do. And that's a
privilege, and so we want peopleto know that. That is, if I had
(34:06):
to argue that there's onedistinct difference between us
and others, is that our commondenominator is data, is
robustness of clinical datasets, and what that is allowing
us to believe about downstreamsuccess. It is not restricted to
a view on a certain vertical ofneuroscience.
John Simboli (34:25):
It would seem that that would take a sophisticated
partner to absorb that andunderstand that. On the other
hand, it would seem it could bebreathtaking in the right
conversation. Is that a fairstatement?
Bruce Leuchter (34:42):
It's a fair statement. I think the ambition
level is high when one tries totackle, you know, an entire
therapeutic area the size ofneuroscience. And what we've
done as an organization isremain relatively lean,
certainly relative to othercompanies heading into Phase 3
studies, and we've done that fora reason. We're certainly fit
(35:03):
for purpose. We've got all thecapabilities and muscle that we
need to progress our programs,but we know that the next
opportunity we work on mayrequire slightly different
expertise, that may require adifferent fit for purpose view
on who we hire and who organizesaround that next project. And
they're going to be plenty ofpeople who organize around all
(35:24):
projects that we take on, butthere may be more bespoke
expertise and capabilities thatare mandated, required in order
for us to succeed in the nextaffiliate co, we've got the
opportunity to bring those folksin. So we don't believe, as I
said earlier in theconversation, no one's good at
everything. Expertise are calledexpertise for a reason. And as
(35:44):
we organize aroundopportunities, we look for the
best expertise that will give usthe highest probability of
succeeding around that affiliateco. And that's what our model
has enabled.
John Simboli (35:54):
If GRIN succeeds the way you hope it will, do you
allow yourself, at this point topicture how transformational
your therapeutic might be, andwhat is the need? What's not
being served? Just how could youchange the equation?
Bruce Leuchter (36:11):
Important question. We believe that we
have an opportunity tomaterially impact the lives of
patients, caregivers andfamilies in a way that hasn't
yet been done. So it is verytrue and important to note that
companies have had significantsuccess around rare pediatric
(36:34):
epilepsies andneurodevelopmental diseases,
particularly over the last 10years, where I would argue human
genetics have enabled moredefinitive diagnosis awareness,
visibility of these diseases hasincreased, and the tide in
general has been rising. But thesuccess to this point has been
largely around treating symptomsof disease, not treating the
(36:56):
underlying disease biology, inthis particular part of the of
the neuroscience universe, wherewe're talking about
neurodevelopmental diseases anddevelopmental epileptic
encephalopathies. Some of thetherapeutic modalities that have
come to the forefront over thelast 5-10, years, gene
therapies, oligonucleotidetherapies, genetic medicines,
are increasingly more oftenputting this on the radar screen
(37:19):
of physicians, KOLs andcompanies, investors, for that
matter, that you can actuallytake a rifle shot, as opposed to
a buckshot, at these diseases.
But as I do think forward todelivering Phase 3 data in GRIN
related NDD, and engaging withregulators around potential
approval and the impact that itmay have on patients, it's not
(37:40):
just the impact that it can haveon GRIN and its families. It's
the impact that it can have fordiseases that are also
genetically defined. If wesucceed in demonstrating that
one can pursue underlyingdisease biology associated with
these diseases, it gives hope,encouragement, motivation,
(38:02):
energy, to doing the same thingacross a number of different
genetically defined diseases forwhich there is no therapeutic
candidate in development, andfor which there is no disease
specific treatment, there isonly an ability to treat
symptoms. And part of what we'retrying to talk to folks about,
irrespective of constituency, isthat creating disease specific
(38:24):
treatments, creating treatmentsthat go after the underlying
disease process and target thatbiology, has to be the way in
which we think about therapeuticdevelopment going forward,
because it's got the greatestchance at delivering the most
pronounced effect size andhelping these patients
maximally. I think if we spendour time, all of our time,
(38:45):
continuing to pursue symptomatictreatments, we leave a lot on
the table that these patientssuffer from. And while we can
see something like seizure, nowyou can actually see a patient
have an epileptic seizure, whatis harder to see is the impact
of the non seizure symptoms onthe patients, the families and
the caregivers and theclinicians who treat them. By
going after the broader diseasestate in the way that we are
(39:09):
with radiprodil in GRIN NDD,we're giving these patients and
all of the associatedconstituencies an opportunity to
target the underlying diseasebiology. And that, I hope, is
catalytic to additional workthat can be done across
additional diseases, where thebona fides are there. We've
shown it can be done, and we getmore momentum to treat these
(39:29):
kids. When I was training inneurology, and I was looking, I
was rotating through pediatricneurology clinics, cynically,
very cynically, you found peoplesaying, particularly those who
weren't going into neurology,that neurology was a "diagnose
and adios" subspecialty. You canmake the diagnosis. It can be a
(39:50):
very sophisticated diagnosticworkup, and it can yield a lot
of information. And then, inessence, you bid adieu, adios
to the patient., Because therejust wasn't anything to treat
them with, right? And we havemost definitely made progress
over the last 30 years in thatregard. But I'd argue there's
been an acceleration of thatprocess over the course of the
(40:10):
last five to 10 years wherethese sorts of disease specific
treatments are now possible,such that no one contemplating a
career in neurology has to everhear "diagnose and adios" again,
because it is not the way Ithink about neurology, and it's
not the way we need to thinkabout neurology today, given all
the technological advancements.
John Simboli (40:32):
Bruce, what's a good partner for Neurvati?
Bruce Leuchter (40:34):
It's a long list, John. There is no favored
nation in our business. We arefocused on the fundamentals
associated with developingneurotherapeutics. That can
happen in a number of differentcontexts. It is certainly true
that large cap biopharmaceuticalcompanies is where we spend a
lot of time. That's where mostof the portfolio reorganization
(40:55):
and some of the strategicshifting occurs that enables
opportunities for externalizingviable technologies. But it's
also true that if you swung thependulum to the other side,
you'd find privately held ormicro cap, small cap biopharma
companies that may be challengedright now by the current market
(41:17):
conditions, may not be able tofinance all the work that they'd
like to do, and may be underpressure to find solutions.
Their technologies may beequally as viable as the
technologies of a multinational,large cap biopharma company. And
then, of course, there'severyone in between. And
everyone in between doesn't justinclude companies. There are
(41:38):
investors in the world who'vechosen to organize around
neuroscience therapeutics andare looking for ways in which to
collaborate, looking for ways toprogress. There are programs
that they've already gottenbehind, but now need some help
with. So we see our audience asa very broad audience. I would
argue that you might include keyopinion leaders and principal
(42:03):
investigators in that audience.
We find ourselves in discussionswith the world's leading
scientists on some of the recentdiscoveries that they've made
that can be mapped on to aclinical thesis surrounding a
certain drug candidate. And thatkind of innovation may not
happen in a wet lab, for us, butcertainly can leverage the work
that does happen in wet labs,and for sure, manage, leverage
rather, the work that these toptier thought leaders are willing
(42:23):
to share with us. So we don'thave a view that our model is
appropriate for a small carveout of the industry. We have the
view that neuroscience iscritically important. It's
important to our industry, butmoreover, it's important to the
world in which we live, wherethe unmet need is sky high, the
viable technologies, whileincreasing in number, are still
(42:47):
not enough. We see the universeis big, and we see it with a lot
of opportunity, and we thinkwe've got the right team
members, the right supporters,the right advisors to help us
succeed in the long term.
John Simboli (43:01):
Thanks for speaking with me today, Bruce.
Bruce Leuchter (43:04):
Thank you, John, it was a pleasure, and I enjoyed
the conversation. Lots ofimportant topics to discuss, and
I'm glad we hit on a number ofthem.
Bruce, welcome to BioBoss.
Bruce Leuchter (00:02):
Thanks, John, pleasure to be here.
John Simboli (00:03):
Bruce, what led you to your role as cofounder
and CEO of NeurvatiNeurosciences?
Bruce Leuchter (00:09):
It draws on a number of different experiences
that I've had over the course ofmy career. And, you know, I grew
up in the home of a brilliantclinician-scientist neurologist,
found my way into neurologyresidency, then did some
training in psychiatry, becauseI felt like I was getting half
the story. So doing bothneurology and psychiatry
broadened my horizons aroundthinking through issues related
(00:32):
to the brain and nervous system.
And from there, I believed thatunderstanding industry, and as
part of that, financial servicesin healthcare and biotech, would
create another dimension to thework that I had done to date,
but use the scientific andclinical perspective, and
frankly, my love of those twodimensions of my life, the
(00:55):
scientific training and clinicalexperience to inform how I
performed my role in thefinancial services sector. And
it was always a third leg of thestool to be able to leverage all
of that in actually operating aneuroscience-focused biotech
company. I think there's nogreater privilege beyond,
perhaps, taking care of patientsthat one can have than
(01:18):
developing a novel therapy for adisease with high unmet medical
need. And that is our mandate atNeurvati, and we get to do it
with best-in-class sponsors,financial partners who help us
along the way. And that'sultimately what led to me
sitting in this seat, which, aswe'll talk about, I'm sure later
on in the discussion, has someunique features to it that draw,
(01:40):
in particular, on the number ofdifferent professional
experiences I've had over time
John Simboli (01:46):
When you were thinking about that, how you
would apply your background andyour interest in, and seeing how
it could turn into, perhaps, atherapy someday, you must have
looked at a lot of differentoptions and a lot of different
possibilities. How did you landon the one that enabled you to
become the co-founder?
Bruce Leuchter (02:06):
Well, I think we in biotech often find ourselves
looking across the landscape ofopportunities. And in many
cases, particularly in theventure world, you find early
stage science, perhaps comingout of a top tier academic
institution, or pre-clinicalassets, molecules that are in
(02:27):
development, pre-clinically thathaven't yet found their way to
the clinic. And then you workyour way downstream and find
clinical data sets around whichyou can organize for
opportunities that exist in themarket. And for our investors,
Blackstone Life Sciences, theclinical data is really
important, and it's importantbecause we focus our efforts on
mid and late stage drugdevelopment, where often
(02:50):
companies find themselves invarious different circumstances
that preclude progressingprograms internally and require
externalizing those programs,putting them in the hands of
entrepreneurs who, in ourcircumstance, have the necessary
amount of capital to finance,they've been in late stage
development. So for us, whilethere is a ton of raw material
(03:14):
out there, early stagetechnologies that hold a
tremendous amount of promise,our mandate is one where we need
to look at mid and late stagedevelopment, and there are some
unique challenges associatedwith that. Neuroscience is a
space that has a prettysignificant capital requirement
to develop drugs throughapproval. Timelines can
sometimes be more prolonged thanother therapeutic areas, and
(03:36):
risk is quite high. And it's notwithout understanding all of
those things that people makedecisions around neuroscience,
product candidates, and for us,focusing on that later stage of
development where we canorganize around data, clinical
data and pre-clinical data thatgive us conviction, is critical
to getting a new affiliate coover the finish line and in our
(03:58):
first affiliate co, GRINTherapeutics, that fact pattern
existed. We had a molecule thathad a significant amount of
clinical data, had a whole lotfor us to look at in terms of
safety, tolerability, dosing,protocol, PK, and even data in
certain neuroscienceindications. And when we coupled
that with GRIN relatedneurodevelopmental disorder and
(04:19):
knew that we could use humangenetics to identify the most
appropriate patient to enroll inour study, and combine that with
the dossier that we had aroundthis program, it made a whole
lot of sense to push off on thisparticular opportunity, and
we've been at it now for fouryears.
John Simboli (04:35):
Does your work put you at the head of GRIN and
Neurvati?
Bruce Leuchter (04:40):
So Neurvati Neurosciences is an operating
company, a development companythat is owned by Blackstone Life
Sciences, and it was created towork on neuroscience
therapeutics across thewaterfront, which means that
we're not restricted to aparticular vertical in
neuroscience. So as an example,right now, GRIN Therapeutics is
(05:02):
focused on neurodevelopmentaldisease, but we look at
opportunities that are in theclinic with critical mass data
that could be in the neurooncology space, could be in the
neurovascular space,neuromuscular space,
neuroinflammatory disease space,neuropsychiatry, pain, sleep,
wake. All of these verticals forus are options, and the lowest
(05:23):
common denominator is whether ornot there's enough data to
support a highly convicted viewaround success in mid and late
stage development and regulatorydiscussions. So what Neurvati
does is operate those affiliateco's, and that's where the
people sit, the human capital,but all of the action, or
activity, if you will, exists atthe affiliate co level. The
(05:45):
Neurvati team drops down intothat affiliate co and executes.
So all of the functions thatyou'd ordinarily expect to see
within a biotech companycertainly exist. They exist at
the Neurvati co level, and thenthe day-to-day execution occurs
in the affiliate co. And that'swhere the asset sits, that's
where the capital flows when weraise capital. That's where the
(06:08):
governance sits, where theincentive structure sits. And it
allows us, as Neurvati, tocontinue to progress this sort
of work across a number ofdifferent projects going
forward. But the project that wehave in hand right now, that
we're solely focused on is GRIN,GRIN related neurodevelopmental
disorder, and the development ofradiprodil to treat these kids
(06:31):
with a really difficult andhighly morbid disease process.
When we look at opportunities,we are focused on human
genetics. We want to haveclarity around the patient
population that suffers from thedisease, how we can identify
those patients, definitivelydiagnose those patients, and
(06:52):
deliver precision therapeuticsto those patients. People define
precision therapeutics invarious different ways, with
various different therapeuticmodalities. But the bottom line
is that we're aiming to usehuman genetics, biomarkers of
all sorts, whether they are fromthe cerebral spinal fluid,
whether they are imagingbiomarkers, electrophysiologic
biomarkers, to try totriangulate around the patient
(07:14):
population that is best suitedto enroll in a study and to
potentially benefit from anexperimental therapy, should it
get approved. And that's exactlywhat we did with GRIN. We said
there's a genetically defineddisease in GRIN related
neurodevelopmental disorder.
There are no drugs approved totreat that disease. There are
drugs approved to treat some ofthe symptoms of that disease,
but no drugs approved to treatthe underlying biology of that
(07:34):
disease. So we can add a lot ofvalue to patients, families and
caregivers, that's key. But wealso want to make sure that
we're going to succeed as bestwe can, as best as one can when
you're developing noveltherapies. So how do we do that?
We look at these triangulationexercises. In our case, GRIN, it
was human genetics, and wedeveloped conviction around our
(07:57):
ability to identify thesepatients, properly diagnose
them, and enrich the patientpopulation that we enroll into
the study. And that gives us ahigher probability of showing a
more impactful clinical effectthat will drive even more
conviction as we head intopivotal studies, which, of
course, is what we're doingright now. So we knew the
(08:18):
biology made sense. We knew themechanistic rationale made
sense, and we knew we couldleverage pretty significantly
human genetics to get us to abetter spot. Historically in the
treatment of these sorts ofdiseases, they're often called
developmental epilepticencephalopathies, or DEEs, or
neurodevelopmental disorders, orNDDs. Typically, you found
(08:39):
companies developing symptomatictreatments. So there may be
seizures that are a componentpart of the disease, they're
developing an anti-epileptic oranti-seizure medicine to treat
those seizures. There may bebehavioral symptoms, and doctors
may use psychotropic medicinesto manage behavioral
dysregulation, but they'retreating the symptom. And what
(09:00):
we thought we could do wasorganize around rapiprodil, a
negative allosteric modulatoragainst the NR2B subunit of the
NMDA receptor, do it in patientswho we definitively know have
hyperactivity at that receptor,given a gain of function
mutation, and potentially driveoutsized effect in those
patients. And we did that in aphase 1b/2A study, a small 15
(09:24):
patient open label data set. Butthe data were so compelling, so
convincing, that despite itbeing open label and a small
number of patients, gave allstakeholders conviction around
the potential therapeuticcandidate. And so we feel like
we've gotten to a mile marker inthe course of our life cycle,
where we've been able to proveout the thesis, where one can
(09:46):
identify an opportunity thatexists within another company,
do a whole bunch of work toconvince ourselves that it's
worthy of the commitment thatwe're aiming to make. License it
in, or acquire the asset indevelop a special purpose
vehicle around it, and that'sGRIN Therapeutics, and then
deliver on data that gives thebroader community conviction
(10:08):
around the potential of the drugcandidate. And now here we are
having done that with GRIN. Andthe aim for Neurvati would be to
reproduce that success acrossanother affiliate co, and, you
know, continue to create aflywheel and become a solution
for neuroscience therapeuticdevelopment, which I'd argue,
and I think most would in thisspace, needs solutions, given
(10:31):
the challenges that are inherentin developing drugs in this
space. There needs to be ways toget creative around how to take
viable technology, resource itappropriately, and deliver it to
patients and caregivers. Andthat's what we're built to do.
John Simboli (10:49):
In that early stage, before you knew you had
traction, an inkling and thedata to support it in the early,
early stages. Sometimes afounder, CEO, goes through a
process of having to leavesomething that feels secure in
order to take on something thatfeels hopeful.
Bruce Leuchter (11:08):
Without question. And it wasn't a new
kind of conversation for me andmy family. I've had it a number
of times at every mile markeralong the way. One experiences,
inevitably angst, wonderingwhether or not the decision is
the right decision. Will ityield success in the way that
(11:30):
the individual experiences it,but also in the way that his or
her family experience it.
There's change, inevitablechange. And I think change can
be disorganizing, destabilizing,anxiety provoking, and it
certainly has applied to me andsome of the career decisions
I've made. But what I've alwayssaid along the way to anyone
who's asked, is life is not adress rehearsal. You know, this
(11:55):
is the real thing. You've gotone chance and go out, learn as
much as you can, put yourself bydesign, in vulnerable positions
where there is clearly risk offailure, but do it in a
controlled way. Do it in a waywhere you've developed enough
muscle mass so that you canleverage it as you're trying to
(12:16):
bob and weave in the new role.
And I would say that it's beenan incredibly enriching
experience to have made thevarious different pivots that
I've made, all of which havecome with a certain amount of
anxiety. But therein lies thelearning. And as I look back and
reflect, I couldn't be happierwith the amount that I've been
(12:39):
able to take on board,synthesize, personalize in my
own way, and then apply toachieving success with a firm,
with academic colleagues beforeI was in the financial services
side of the business and nowwith the best in class team. And
assuming ,you know, thatleadership role has a ton of
gravity attached to it. And itisn't just your own personal
(13:03):
experience and your testing ofyour ability to pivot. It's
supporting the company, leadingthe organization, creating the
kind of culture, that enablespeople to want to sacrifice, to
want to compete, to want to lockarms, and who believe that one
plus one equals three. Andthat's the beauty of a biotech
(13:25):
company, because the expertiseare so diversified across the
team, lots of advanced degreepeople, plenty who don't have
advanced degrees, who areequally as smart and capable and
they have expertise that allcontribute to the ultimate
success of the organization. Andto the earlier comment on data
(13:46):
being binary, you progressprograms for years and years
with countless amounts ofinvestment dollars, and the fate
of the program oftentimes hingeson a data point, maybe two,
depending on how many pivotalstudies you're running. Why
would people do that? Why wouldpeople take on that binary risk?
(14:06):
And the answer isn't, in mymind, because there's economic
upside if you succeed. Theanswer is that in so doing, in
all of the blocking andtackling, the sausage making,
you are coalescing as a reallysharp, capable, intelligent
group of people, and the sum isgreater than the parts, and it's
(14:30):
a living, breathing creature.
You have to want a lot ofactivity and fire drills and
things that need to get solvedfor on a daily basis in order to
like this job. But if you wantit, you will love the job,
because there's all of that andthen some. And if you succeed,
you've succeeded because you'vegotten folks to believe that the
team that's being brought tobear on this particular project
(14:53):
is a team that can't be beat.
And it's not so much beingbeaten by other people or other
companies. It's about winning incoalescing as a group and
delivering results thatinevitably benefit the
communities you're trying totreat. In the event that you do
not succeed in getting a drugapproved, you have certainly
(15:17):
succeeded in giving hope topatients who've participated in
the study, patient advocacyorganizations who haven't had as
much visibility prior to yourengagement around their disease,
the relationships that you'vebuilt, the education that you've
provided to all stakeholders.
It's beneficial net, net, to besure, and I think you've got to
want that to embrace this, youknow this, binary risk that
(15:39):
floats above all of our heads.
John Simboli (15:45):
When I first started doing the podcast, I was
physically going to executivesoffices and bringing my kit and
doing this, and then during thethe, you know, the pandemic, of
course, I found this format thatwe're working in today worked.
And one of the things I foundthrough that discussion was I'd
be talking, you know, across akitchen table, you know, 11
(16:08):
o'clock at night with someoneand and they, the family, would
pass through the frame, someonefrom the family passed through.
And it led to this discussionabout what it is that a CEO does
at a biopharma company. Sohere's what I'm trying to get
at, an executive at a big pharmacompany, people probably have a
certain idea of what that job islike. It's probably very much a
(16:28):
managerial job, because it's abig thing. And then people
probably have a rudimentary ideawhat a scientist does. And they
picture being in the lab. Whatis your day like? When someone
says to you, what do you do fora living? How do you try to
explain that? How does your daygo by?
Bruce Leuchter (16:46):
Well, the easiest answer, and I get that
question all the time, is I tryto develop novel therapies for
diseases of the brain andnervous system. I think most
people can get that. What theydon't necessarily get is how you
do it on a day to day basis. Andthe diversification of
experiences that I am able tohave, need to have on a daily
(17:09):
basis, is just what the doctorordered. So at any given moment
in time, I may be knee deep inan HR related issue, and there
are all sorts of considerationsthat one needs to bring to bear,
most of which require some levelof mindfulness and self
awareness and solution orientedthinking, and that has nothing
to do with developing drugs, perse, it's about developing people
(17:32):
and managing people, which, as Imentioned in my last comment, is
critical to the success of abiotech company. In the next
hour after that heavy duty HRmeeting, I may find my way into
a clinical development meetingtalking about clinical trial
design, and now I get to put onmy neuroscience cap and think
(17:53):
about biology. Think aboutdisease states, think about
physician behavior. It'sgratifying, it's intricate, and
it's a big part of what I do. Inthe hour following that meeting,
I may find myself talking toinvestors who may have macro
concerns about the market or thebroader neuroscience space, and
(18:17):
wonder how our business isaccounting for those macro
developments. They may be justas much in the weeds on the
micro topics, at which point I'mtalking about the science that
we're progressing and theclinical work that we're doing
in a way that is well receivedor can be well received by an
investor who's thinking aboutdeploying capital into an
(18:38):
investment. In the hour afterthat, I could find myself on the
line with investment bankers whoare wondering whether the IPO
markets will reconstitute, andare thinking about the fate of
emerging growth biotechcompanies in the world we
currently live in, and all thedifferent three dimensional
(19:00):
chess that one needs to playaround that as we try to fund
the companies that couldpotentially deliver these
treatments to patients, it's therichest of experiences. And for
people who do like to bob andweave, which is the terminology
I tend to use, there's plenty ofit in this role. I think it
keeps you sharp. I think youhave to care not just about any
(19:22):
particular function, but aboutthe broader organization. And
you've got to care about yourstakeholders. Because as much as
you're managing a team of highlycapable, gifted people on the
operating side, you're managinga team of highly capable, often
highly successful people on theboard front, and there's a lot
of considerations that surroundthat too. We are in the
(19:43):
fortunate position at NeurvatiGRIN of having just a tremendous
board of directors with peoplewhose experiences range across
the industry in all sorts ofsenior leadership roles, and we
benefit from that mind share ona daily basis. But that too
requires management So peopleoften say that the CEO role is a
lonely role. If I've heard thatfrom one person, I've heard it
(20:05):
from 1000. And to some extentthey're right about that.
There's one person in charge ofwhat I'm in charge of. But I
don't see it as an N-of-1exercise, where one might think
about loneliness existing in anN-of-1 world. I see it as an N
of infinity world, because inany given moment, whether it's
an employee, whether it's theexecutive leadership team, it's
(20:26):
a vendor, aan investor, abanker, a consultant, a
stakeholder at the board level,there's constant dialog,
constant thought experiments andconstant solution oriented
thinking. And that doesn't makeme feel lonely at all. You have
to want to go out and get it andnot believe that you don't need
it. I think if there's one thingthat everyone should learn about
(20:46):
this role is that moreperspective, more information,
you know, more mind expansionequals higher probability of
success, and you want to take asmuch of that on as you possibly
can. It requires a healthy egoto do it, but it is definitely
beneficial, so I don'texperience the sort of classic
loneliness that folks talkabout. That doesn't mean the job
(21:10):
isn't challenging,psychologically. Of course, it
is when you're thinking aboutall the different roles and
responsibilities that the CEOplays. But I'm in the fortunate
position of working with thebest people in the industry, no
matter who we're talking about,stakeholders, or the executive
leadership team, or or any givenperson in the company. And for
me, that's a big win.
John Simboli (21:29):
Your phrase "bob and weave" catches my ear, and I
don't want to strain themetaphor, but it certainly
brings to mind the image of aboxer and someone who knows how,
through their footwork, toapproach the moment and when to
back off. So to follow thatanalogy, when you close, when
you come in and really engage onsomething, how do you know when
(21:54):
to do that and make whateverdecision you have to make as a
CEO, versus when to disengage,go back to what you just spoke
about, bringing in all theinformation and try to evaluate
it. I imagine it's a neverending, in and out, back and
forth. But how does one do that?
Bruce Leuchter (22:10):
Well, I think no one should believe that there is
ever a perfect decision. And Ithink if you convinced yourself
of that and you're out trying tofind it, it may amount to a bit
of a wild goose chase. And thebobbing and weaving isn't so
much evasion of differentopinions, personalities,
(22:34):
decisions, etc. It's morenimbleness, you know, light on
your feet, figuring out how tomove and change with the daily
changing environment in which welive as biotech folks. And
because there is no perfectdecision, it's about
triangulating around the bestdecision. And if you allow
(22:56):
perfect to be the enemy of thegood, you may never find that
decisive moment. You may alwaysbe sitting there ambivalating
about what it is that's best forthe company. But if you take on
these different vantage pointsand you appropriately
contextualize them based on thesource from which it's coming, I
think it gives you enoughinformation to ultimately come
(23:19):
to a conclusion that is best forthe company, that you believe
wholeheartedly is going to yieldthe most amount of success, and
recognize that there are goingto be challenges associated with
that decision more often thanthere isn't. And as long as
you're prepared to contend withthat, you can remain light on
your feet. You can continue tobob and weave. It's probably
important to think about bob andweave in the way that I do,
(23:42):
which isn't so much trying tosidestep problems, you know,
trying to bounce around andevade a punch. It's more about
trying to get the rhythm of thebusiness, trying to get, trying
to understand the people thatyou're working across from or
next to, and incorporate theirstyle into what it is that you
need to accomplish. Because itis not monolithic. It is not an
(24:05):
N equals 1 role, and it is onethat requires onboarding the
kinds of perspectives that youperhaps don't have but need to
quickly understand to get to theright decision.
John Simboli (24:19):
When you were a kid, can you picture thinking
I'd like to be this when I growup? Did the this turn out to be
that? What you're doing? Or isthis something else?
Bruce Leuchter (24:29):
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 seewas a lot of neurology. And, you
know, I had the great fortune ofgrowing up in the home of a
brilliant clinician scientist,neurologist, the best doctor
(24:50):
I've ever known, really talentedphysician, and saw the work that
he was doing on a daily basis.
You know, before the advent ofdigital technologies and the
like. EEG pages strewn acrossthe kitchen table, CSF samples
in the freezer getting ready togo back to the office on Monday,
go on rounds in the hospital ona Saturday, and saw it
firsthand. Thought it was thecoolest job in the world and the
(25:13):
most privileged relationshipthat one could develop in the
world. For someone who wasinterested in academics and
science, there, in essence, wasno other path. So while I can
represent to you that becoming aphysician was the narrow view I
had of my career dating back toas early as I can remember, I
(25:34):
can also represent to you that Ifelt pretty early on that there
may be more to it than takingcare of patients, as much of a
privilege as that is. It feltlike the ecosystem was bigger
than that, the broader ecosystemof healthcare. I have a hard
(25:56):
time articulating it moreclearly, because I don't think I
understood it any more clearlyback in the day, but it did feel
like there were other forces atplay that were ultimately
determining how a patient wastreated by their physician, and
that got me interested inmanaged care. I did some work at
an HMO back in medical school. Isaw pretty early in coming to
(26:18):
New York City to train that, youknow, you throw a stone, you hit
two bankers in New York City andgot close to Wall Street, but at
a moment in time at which therewas an enormous amount of novel
therapeutic development. This isthe novel anti-epileptics, the
novel MS drugs, the pain drugs,the sleep drugs, all the stuff
we currently use to treatpatients, was happening at that
(26:39):
moment in time, and there wasjust a demand for viewpoints
from people who were inphysician roles or academic
roles. I found my way to that,and that snowballed, and here I
am. But again, the governingprinciple being, I like to learn
and I like to challenge myself,and I believe that humility is
critical, and I believe thatvulnerability is critical to
(27:01):
learning, believe it or not,allowing yourself to feel
vulnerable. And that I thinkI've believed for also as long
as I can remember, so maybethere is a common thread. But at
the end of the day, I was theson of a brilliant physician,
and I was beelining straight tomedical school.
John Simboli (27:21):
who is Neurvati Neurosciences?
Bruce Leuchter (27:23):
I tell people, our job is to identify and
develop novel therapeutics fordiseases of the brain and
nervous system. I think mostpeople, whether they're close to
biotech or far from it,appreciate that, understand
that. We do it in a way that isdifferent than a standard
(27:44):
biotech company does, just givenour relationship with Blackstone
Life Sciences, how they financethe work we do, and how they
partner with us on it. Alsodifferent in terms of the way in
which we innovate, where we lookfor programs that are going to
be externalized from establishedcompanies, determine whether or
not there's any hazard aroundthat decision to externalize.
(28:06):
Often there is not. Often thereis just the need to prune
portfolios, to rethinkstrategies in certain
therapeutic areas, less of acommentary on an individual
program, more of a commentary onan overarching corporate
strategy. And we, because of ourrelationships, both at the
Neurvati co level, giveneverything that each of the
(28:27):
senior leaders have done intheir careers, and at Blackstone
Life Sciences, the network isquite large, and so we find
ourselves in bespokeconversations with the world's
largest pharma companies and,for that matter, small privately
held pharma companies or biotechcompanies, where there is a
need, there is a need foroperational expertise, there is
a need for alternativefinancing. And we identify those
(28:48):
programs, we diligence them inan incredibly robust way, in a
manner that I'm quite proud of,the level of detail, the embrace
of the science, theunderstanding of the clinical
development that we need to do,the regulatory path that we'll
pursue, the markets that we aimto target, and then we find our
way toward establishing a newspecial purpose vehicle, or
(29:10):
affiliate co and thenprogressing it into late and
through late stage developmentto approval. So again, the
easiest way to say it is wedevelop neuroscience
therapeutics, and we do it in away that leverages the
operational capabilities that wehave and the financial backing
that we have from our partner,
John Simboli (29:27):
Let's say that at an investor conference, and you
begin to give the description ofwho you are as a company, as
you've been giving it to me, andyou get that moment when someone
wants to put your company, intoa particular category. And
sometimes it's the right one,sometimes it's wrong one. It's
been my experience that oftenthe CEO's job is to help to
(29:48):
educate at that point so thatyou know they don't get stuck in
the wrong spot. So are therewrong spots that Neurvati would
get placed into? And if thereare, what are they? What is that
pattern? And then how do youhelp get out of that pattern?
think
Bruce Leuchter (30:05):
I think our model requires explanation.
Because as much as we developmid to late stage therapeutics,
there are unique features that Ithink people need to understand,
for them to fully appreciatewhat our mandate is and how we
do it. We certainly want peoplefocused on the affiliate co work
that we do, particularly wherewe are right now with GRIN
(30:27):
Therapeutics, heading into aphase three study, there's all
kinds of motivation aroundeducating the stakeholder,
community, investors, strategicsand others, on how promising
this development stagetherapeutic is and how focused
we are on progressing the balldown the field and gaining
approval, ultimately, anddelivering it to patients. So we
want the spotlight on theaffiliate co. But we also want
(30:50):
people to understand that awayfrom the affiliate co are all of
these capabilities that can beleveraged against a very broad
swath of neuroscience. I thinktypically when people think
about biotech companies, theythink about those companies
pursuing perhaps one or twoverticals within a given
(31:11):
therapeutic area. So if you'redeveloping a drug for
psychiatric indications, youlikely organize around
additional psychiatricindications. If you're
developing a drug against aneuroinflammatory disease,
you're organizing around broaderneuroinflammatory diseases or
adjacent indications. And what'sdifferent about us is that we
are not restricted to a givennumber of verticals. It's really
(31:32):
important that people understandthat, because what we want folks
to appreciate is that we havethe ability to look across the
waterfront of neuroscience, andeven though we are sitting here
today talking aboutneurodevelopmental disease for
GRIN Therapeutics and wantingpeople to understand what it is
that we do around radiprodil inthese diseases, we also want
(31:53):
people to realize that if thereare opportunities away from
neurodevelopmental disease oraway from orphan neurology that
are focused on sleep/wake as anexample, or focused on pain, or,
for that matter, neuro oncology,glioblastomas, or malignant
brain tumors, that we have anopportunity because of our
(32:15):
sponsor, to go think about thosediseases, apply the same amount
of rigor, deliver the same kindof best-in-class work product
around its viability, and if weget there, pursue it, even
though one would argue thatneuro oncology is very different
than neurodevelopmental disease.
And we think that's okay,because, in our view, what the
space really needs is championsfor viable drug candidates,
(32:39):
viable therapeutic candidates.
It needs to have people who arewilling to roll up sleeves, get
into the weeds, make carefuldecisions around what's best for
any given program, and not berestricted to a given vertical
within neuroscience. Because atthe end of the day, we want to
(32:59):
take clinical stage productcandidates, properly resource
them, deliver the ultimate datapoint, gain approval, and find
our way to patients throughwhatever mechanism. Could be us
commercializing the drug. Couldbe us putting it in the hands of
a vertically integratedorganization that is already
commercializing against the samecall point, against the same
(33:22):
position. And what we've noted,this is a very generic comment
to all of our peers across thebiopharma landscape., but what
we've noted is that it's notalways true that you can work on
everything that you want to workon. And in some cases, despite a
product candidate beingperfectly viable, fundamentally,
there are reasons for companiesto externalize or terminate
(33:45):
their own resource allocationagainst that program. And
because we're not restricted toany of these given verticals,
per se, we can take that robustdata set and we can create value
around it. We can progress theball down the field in a way
that one may not have otherwisebeen able to do. And that's a
privilege, and so we want peopleto know that. That is, if I had
(34:06):
to argue that there's onedistinct difference between us
and others, is that our commondenominator is data, is
robustness of clinical datasets, and what that is allowing
us to believe about downstreamsuccess. It is not restricted to
a view on a certain vertical ofneuroscience.
John Simboli (34:25):
It would seem that that would take a sophisticated
partner to absorb that andunderstand that. On the other
hand, it would seem it could bebreathtaking in the right
conversation. Is that a fairstatement?
Bruce Leuchter (34:42):
It's a fair statement. I think the ambition
level is high when one tries totackle, you know, an entire
therapeutic area the size ofneuroscience. And what we've
done as an organization isremain relatively lean,
certainly relative to othercompanies heading into Phase 3
studies, and we've done that fora reason. We're certainly fit
(35:03):
for purpose. We've got all thecapabilities and muscle that we
need to progress our programs,but we know that the next
opportunity we work on mayrequire slightly different
expertise, that may require adifferent fit for purpose view
on who we hire and who organizesaround that next project. And
they're going to be plenty ofpeople who organize around all
(35:24):
projects that we take on, butthere may be more bespoke
expertise and capabilities thatare mandated, required in order
for us to succeed in the nextaffiliate co, we've got the
opportunity to bring those folksin. So we don't believe, as I
said earlier in theconversation, no one's good at
everything. Expertise are calledexpertise for a reason. And as
(35:44):
we organize aroundopportunities, we look for the
best expertise that will give usthe highest probability of
succeeding around that affiliateco. And that's what our model
has enabled.
John Simboli (35:54):
If GRIN succeeds the way you hope it will, do you
allow yourself, at this point topicture how transformational
your therapeutic might be, andwhat is the need? What's not
being served? Just how could youchange the equation?
Bruce Leuchter (36:11):
Important question. We believe that we
have an opportunity tomaterially impact the lives of
patients, caregivers andfamilies in a way that hasn't
yet been done. So it is verytrue and important to note that
companies have had significantsuccess around rare pediatric
(36:34):
epilepsies andneurodevelopmental diseases,
particularly over the last 10years, where I would argue human
genetics have enabled moredefinitive diagnosis awareness,
visibility of these diseases hasincreased, and the tide in
general has been rising. But thesuccess to this point has been
largely around treating symptomsof disease, not treating the
(36:56):
underlying disease biology, inthis particular part of the of
the neuroscience universe, wherewe're talking about
neurodevelopmental diseases anddevelopmental epileptic
encephalopathies. Some of thetherapeutic modalities that have
come to the forefront over thelast 5-10, years, gene
therapies, oligonucleotidetherapies, genetic medicines,
are increasingly more oftenputting this on the radar screen
(37:19):
of physicians, KOLs andcompanies, investors, for that
matter, that you can actuallytake a rifle shot, as opposed to
a buckshot, at these diseases.
But as I do think forward todelivering Phase 3 data in GRIN
related NDD, and engaging withregulators around potential
approval and the impact that itmay have on patients, it's not
(37:40):
just the impact that it can haveon GRIN and its families. It's
the impact that it can have fordiseases that are also
genetically defined. If wesucceed in demonstrating that
one can pursue underlyingdisease biology associated with
these diseases, it gives hope,encouragement, motivation,
(38:02):
energy, to doing the same thingacross a number of different
genetically defined diseases forwhich there is no therapeutic
candidate in development, andfor which there is no disease
specific treatment, there isonly an ability to treat
symptoms. And part of what we'retrying to talk to folks about,
irrespective of constituency, isthat creating disease specific
(38:24):
treatments, creating treatmentsthat go after the underlying
disease process and target thatbiology, has to be the way in
which we think about therapeuticdevelopment going forward,
because it's got the greatestchance at delivering the most
pronounced effect size andhelping these patients
maximally. I think if we spendour time, all of our time,
(38:45):
continuing to pursue symptomatictreatments, we leave a lot on
the table that these patientssuffer from. And while we can
see something like seizure, nowyou can actually see a patient
have an epileptic seizure, whatis harder to see is the impact
of the non seizure symptoms onthe patients, the families and
the caregivers and theclinicians who treat them. By
going after the broader diseasestate in the way that we are
(39:09):
with radiprodil in GRIN NDD,we're giving these patients and
all of the associatedconstituencies an opportunity to
target the underlying diseasebiology. And that, I hope, is
catalytic to additional workthat can be done across
additional diseases, where thebona fides are there. We've
shown it can be done, and we getmore momentum to treat these
(39:29):
kids. When I was training inneurology, and I was looking, I
was rotating through pediatricneurology clinics, cynically,
very cynically, you found peoplesaying, particularly those who
weren't going into neurology,that neurology was a "diagnose
and adios" subspecialty. You canmake the diagnosis. It can be a
(39:50):
very sophisticated diagnosticworkup, and it can yield a lot
of information. And then, inessence, you bid adieu, adios
to the patient., Because therejust wasn't anything to treat
them with, right? And we havemost definitely made progress
over the last 30 years in thatregard. But I'd argue there's
been an acceleration of thatprocess over the course of the
(40:10):
last five to 10 years wherethese sorts of disease specific
treatments are now possible,such that no one contemplating a
career in neurology has to everhear "diagnose and adios" again,
because it is not the way Ithink about neurology, and it's
not the way we need to thinkabout neurology today, given all
the technological advancements.
John Simboli (40:32):
Bruce, what's a good partner for Neurvati?
Bruce Leuchter (40:34):
It's a long list, John. There is no favored
nation in our business. We arefocused on the fundamentals
associated with developingneurotherapeutics. That can
happen in a number of differentcontexts. It is certainly true
that large cap biopharmaceuticalcompanies is where we spend a
lot of time. That's where mostof the portfolio reorganization
(40:55):
and some of the strategicshifting occurs that enables
opportunities for externalizingviable technologies. But it's
also true that if you swung thependulum to the other side,
you'd find privately held ormicro cap, small cap biopharma
companies that may be challengedright now by the current market
(41:17):
conditions, may not be able tofinance all the work that they'd
like to do, and may be underpressure to find solutions.
Their technologies may beequally as viable as the
technologies of a multinational,large cap biopharma company. And
then, of course, there'severyone in between. And
everyone in between doesn't justinclude companies. There are
(41:38):
investors in the world who'vechosen to organize around
neuroscience therapeutics andare looking for ways in which to
collaborate, looking for ways toprogress. There are programs
that they've already gottenbehind, but now need some help
with. So we see our audience asa very broad audience. I would
argue that you might include keyopinion leaders and principal
(42:03):
investigators in that audience.
We find ourselves in discussionswith the world's leading
scientists on some of the recentdiscoveries that they've made
that can be mapped on to aclinical thesis surrounding a
certain drug candidate. And thatkind of innovation may not
happen in a wet lab, for us, butcertainly can leverage the work
that does happen in wet labs,and for sure, manage, leverage
rather, the work that these toptier thought leaders are willing
(42:23):
to share with us. So we don'thave a view that our model is
appropriate for a small carveout of the industry. We have the
view that neuroscience iscritically important. It's
important to our industry, butmoreover, it's important to the
world in which we live, wherethe unmet need is sky high, the
viable technologies, whileincreasing in number, are still
(42:47):
not enough. We see the universeis big, and we see it with a lot
of opportunity, and we thinkwe've got the right team
members, the right supporters,the right advisors to help us
succeed in the long term.
John Simboli (43:01):
Thanks for speaking with me today, Bruce.
Bruce Leuchter (43:04):
Thank you, John, it was a pleasure, and I enjoyed
the conversation. Lots ofimportant topics to discuss, and
I'm glad we hit on a number ofthem.
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