April 20, 2024 • 49 mins
Erik Buntinx, founder and CEO of ANeuroTech, shares his thoughts with BioBoss host John Simboli about leadership in biopharma and how ANeurotech is working to develop effective treatments, with minimal or no side-effects, for patients who suffer with depression
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
John Simboli (00:00):
Today I'm speaking with Erik Buntinx, founding CEO
(00:03):
of ANeuroTech, headquartered inAlken, Belgium. Welcome to
BioBoss. Erik.
Erik Buntinx (00:09):
Many thanks, John, to give me the floor. We hope to
have a very interestingconversation.
John Simboli (00:13):
What led to your role as founding CEO of
ANeuroTech?
Erik Buntinx (00:18):
Well, John, I'm very happy with your question
because this is a very personalstory. So my role as founding
CEO is something that came like. . . I was a clinician,
already in my residence years inLeuven, Maastricht years,
studying on depression. Idetected some new mechanisms
that could improve theantidepressant effect in
(00:40):
treating patients. And based onthat concept, I went to some
very well known people such asDr. Paul Janssen, founder of
Janssen Pharmaceutica, toexplain my idea and he was so
enthusiastic that he allowed meto go into his library on all of
these molecules that hesynthesized. And I looked into
(01:02):
that library, I see myself stillsitting in that small room with
all these papers, and all thesebooklets and looking for a
compound that corresponds tothat pharmacological idea and
just found one. And that's thestarting point of being a
founding CEO. I found thatcompound, I could file a patent
(01:24):
on it. And I founded, then, myfirst biotech company, where we
developed that drug in relationto treating depression. I
started with science, withclinical concepts. And went into
the business, raising money.
I've raised, up to date, morethan 25 million euro. And my
board was then asking me, Erik,what do you think about becoming
(01:47):
a CEO? I said, I'm a scientist.
similarly, This was really notrealistic. I mean, coming from
myself and confirmed by others.
But just before I went into thatrole, I got pretty sick. And I
(02:09):
said to these guys, at my board,look, this will not work because
I have to undergo a very seriousoperation. And they say "No, no
problem, Erik when you're readyother coming out of the clinic,
you're welcome." And I went outof the clinic with still some
tubes in me and I see myself atthe first board meeting, where I
was unconfirmed as CEO. Sothat's a little bit of my story
(02:34):
on that.
John Simboli (02:38):
Do you recall, when you had your meeting with
Dr. Janssen, that must have beendear to his heart, because your
research apparently was verymuch something he'd been working
on, something he was interestedin. What did he think when you
came in to talk to him?
Erik Buntinx (02:53):
You have to know I was introduced to him by a very
good friend of mine, which wasDr. Paul Stoffels. He became
afterwards head of R&D atJanssen. And this friend studied
together with me, and he said,"Look, you have to talk with
Paul." And I thought, I willexplain to him the idea and then
Paul can take that forward inhis R&D environment. That was
(03:17):
the idea. So I was very humbledto go to tell something, but
Paul was listening. And healways has been somebody who is
intrigued by "Where's the value?
What is here to make a success?"And his reaction after my
explanation was, "Oh, EriK, Iwill not do that. You have to do
that. That's your drug. And youhave to build a company on
(03:37):
that." I never thought aboutthat. But he said "You have to
go back home. Talk with yourwife, and tell the story." This
was so convincing, that fromthat moment on there was only
one objective and that's mebuilding a company, becoming,
also the founder and the CEO,And he has always supported me
(03:59):
and that's respected.
John Simboli (04:03):
It sounds like as high a compliment, as one could
pay to you to say this hasmerit, go build it. On the other
hand, it was probably dauntingto be confronted all of a sudden
with this idea (04:14):
Oh, I've got to do this.
Erik Buntinx (04:16):
Yes, indeed. And I was wondering why he replied
like that to me. I learned fromPaul, I discussed further with
him. And he explained me to methat when you do this research
work and also this business,what is absolutely key is that
John Simboli (04:32):
Let me ask you about the evolution from
the person, the guy, who mostbelieves it, he has to do it,
because that belief will playdown in the realization and the
success. I think he thought,this we may not take away from
him, from Erik, he's theinventor, he has seen this. He
(04:53):
is a clinician, he knows theins and outs, he has tried this
already in his clinic. So heknows all about it. So that is
the treasure that you have toexplore. Because in biotech and
developing drugs or treatmentsin patients, this is not only
mathematics, it's not a kind ofcalculation. It's a dynamic
(05:18):
process where you have tobalance everything. And to
appreciate what is important,what's not important. And that
brings your product further.
scientist to entrepreneur tobuilding a company to trying to
(05:38):
bring therapeutics to patients.
So at what point did you realizethat you had the entrepreneurial
determination or energy to wantto go out and suggest to
someone, "Hey, I have an ideahere?"
Erik Buntinx (05:51):
I must say this was appealing to own background,
personal background. So alreadyas a child, I was somebody who
was very, very driven with,let's say, a kind of explorer
attitude. And when I was eight,I think a teacher asked me,
"What do you want to be in yourlife?" I said "An astronaut, of
(06:12):
course, I want to explorespace." And I want to go for
these endeavors. And also, as anexample, while I was 12, I was
interested in astronomy, andthen I went to my parents, who
didn't know anything aboutscience. They were farmers, in
fact. And I say, I want to buy atelescope. They're really
(06:36):
shocked. So Oh, my God, what ishappening here? I was driven by
science, but entrepreneurship,doing something, building
something up. So always tryingto realize things. So that is
still in my blood, I think. Andthen you go for medicine
studies, which is not reallyentrepreneurial oriented, of
(06:59):
course, it's more about gettingknowledge, know-how, training,
clinical work, academic work,which I did. So I was then a
little bit away from myentrepreneurial drive. However,
it was always playing in myhead, in my background. And
that's also the reason why Ihave not become, finally, an
academic. I was a researchfellow at University of
(07:22):
Maastricht, where I indeeddiscovered my hypothesis, and
the foundations of ANeuroTechhas been there. But that was
pretty successful. I mean, thatresearch work, and the
professors proposed for me tobecome an academic, and to go
for a chair. And it was yes,it's very attractive. I was in
(07:43):
residence then,, but this wasnot aligned with my personality.
And I had a very good friend,who was pretty much older, I
think, 15 years older than me,he was, in fact, my insurance
agent. I have good contact withhim. He was also admiring what I
was doing. And I asked him, Whatdo you think about it? "Oh, no,
(08:05):
it's very clear, he said, Younever may be become an academic.
You will be unhappy all yourlife." And I explained to him
about my ideas, of course. Andhe said, "Yeah, that's your
way." And really, I took that. Isaid, Look, that's clear. There
is no reason why he would adviseme, without reason. And so I
(08:30):
went for my privateendorsements, I founded my own
outpatient clinic where bigclinical research center was
integrated. So we are currentlydoing very many clinical trials,
sponsored. We are one of thebiggest privately owned clinical
research centers in Europe. Andwithin that framework, I
developed, further, myhypothesis. I discovered that
(08:52):
work, with Janssen, I broughtthat into my research center, we
did further research so that wecould develop IP and so on. So
you see, this is a veryentrepreneurial background,
mentality. And I think I got itfrom my parents. They were
farmers and you know, a farmeris in fact, a real basic
(09:13):
entrepreneur. You have to workon your field, on your animals,
every day. Look what you can dokwhat you can do better.
Otherwise, you will you will godown and this is a dynamic. I
cannot miss.
John Simboli (09:25):
I never thought of it quite like that. There's no
guarantee to being a farmer,right?
Erik Buntinx (09:29):
There's also another story on that because
when I was around 14, my fatheralso tried to do new things. I
don't know how it wasn't in theU.S.,but here in Europe in this
year, we are talking about75-76, strawberries were coming
(09:49):
up as delicacy. And my fatherthought, maybe we have to do
that and I joined him and nobodydid that. We built up a
strawberry farming business thatdid very well. And I did that
with him for four years.
John Simboli (10:08):
Yes, that's an entrepreneurial background. It's
interesting. If we went back towhere you were just a moment
ago, and if your friend who'syour insurance agent, were here
and I said to him, "What was itabout Erik's personality that
made you know, right away, no,this is this is what I see."
(10:30):
What would he say? Whatcharacteristics do you think he
saw in you at that time?
Erik Buntinx (10:35):
That I'm always driven by my ideas, and that I'm
a happy man when I can work onmy ideas, that's for sure. And
that I will be unhappy when Ihave to work on ideas from
others.
John Simboli (10:49):
So you're having a conversation with Dr. Janssen,
and, he said, in effect, itsounds like, this is an
interesting idea, time for youto go home and talk with your
wife and and break the bad newsthat you're going to start a new
company. Do you remember whatthat was like? Was that an okay,
part of your development andyour growth? It's not an easy
thing to do? I wouldn't think.
Erik Buntinx (11:11):
At first, I had the feeling I'm here in a
fantasy, because you have toknow I didn't have any
experience in the form ofbusiness, at all. I didn't know
really what a pharmaceuticalcompany was. I didn't know
anything about raising money,private equity, all of these
things. And there is then thebig Dr. Paul Janssen, who is
(11:34):
absolutely a hero in the world,who is then saying, to me, and I
didn't know him. That was thefirst time I met him. Erik, you
have to go for your own pharmacompany. I came home, I'd said,
Look, maybe this is somethingmad. What is this, an illusion?.
(11:55):
So I had to digest it. Luckily,I was had a good friend, Paul
Stoffels, who knows ins andouts, of course already then,
and other persons we are stillwith me, all these guys said,
yeah, you have to do it. Andeven better, we will join you,
we will support you. So yes,really interesting. And so just
(12:21):
you have to know the situationthat I'm the CEO of a group,
leading a group of people whohave extremely in-depth
experience as experts in thisfield. While I'm coming, in
fact, from a kind of naiveposition. Step by step, I
realized that then I was advisedby my friends to go to an IP
(12:44):
lawyer. I've never heard aboutan IP lawyer. I just went to the
clerk, which is still my IPlawyer, and I said, "Look, I
have to tell a story." And Itold the story. And the first
question, "I will ask you onequestion. Have you ever told
anybody about this?" No. Only myfriends." "Then we are okay,
(13:07):
then we will follow the path".
And yes,, for my personalenvironmental, my wife, etc. My
wife has known me from when wewere 17. So that's, I think,
also very important. And alreadythen, as I told, I was very
entrepreneurial, I did thingsother kids didn't do. I owned my
money, et cetera. So of course,it was a shock for her but it
(13:32):
was also not surprising, at all.
John Simboli (13:37):
As I hear you tell the story I picture two words
that are very similar butthey're very different. So dream
and dreamer. To have a dream,can be a creative act. And it
helps people accomplish thingsthey couldn't even imagine. To
be a dreamer, we think ofsomeone who may never accomplish
those things. Maybe that'sunfair to make it be that
(13:58):
simplistic. But did you know youhad a dream? Did you know you
were not a dreamer?
Erik Buntinx (14:05):
Yes, the dream, of course, of being able to bring
medicine to patients sufferingfrom depression, and that's very
personal because in my familyfrom the mother's side, we had a
lot of people suffering veryheavily from depression,
including suicide. So I wasalready focused on that. But
then thinking that you couldbring a treatment to all these
(14:28):
suffering patients that you havediscovered. Yes,, that's that's
a legacy that give your lifemore worth I think, that's
certainly, absolutely the dream.
But no, I'm not a dreamer. I'malso not a romantic and I think
that's the difference. I have adream, or several dreams, let's
say, but immediately I try tocheck. How can you realize that?
(14:49):
What do you have to do inreality? How does the world work
or the systems work to getsomething done? So, very focused
on these kind of logisticbusiness related concepts. And
that's, I think, an opposite toa dreamer, because a dreamer
doesn't want to do that realitycheck, because then the dream
(15:12):
gets less attractive.
John Simboli (15:18):
When you were negotiating, or maybe that's not
the right word, when you wereworking through that mixture of
creative spark, and idea andrealizing that the next step was
to build something, you probablyhad a pretty good idea as a
logical, rational, scientificmind, what it was that needed to
(15:38):
be done to begin the process ofbuilding a company. But the CEOs
I've spoken with many of themwho are founders, also would
have said to me on BioBoss, as afirst-time CEO I didn't know
what I didn't know, that sort ofthing. So when you pictured what
it would be like, in the verybeginning, first few weeks,
first few months of building acompany, what was that picture?
(16:00):
And then what was that reality?
What was the difference orsimilarity?
Erik Buntinx (16:05):
Why, indeed, starting from this dream, and
you think, yeah, once I canconvince people to invest in it,
and to join also the team, thatthey join your dream, and that
they go on with that story. But,of course, people are people.
And what you then see is thatonce they are there, and sitting
(16:27):
at your board, for instance arein your team, then they are also
popping up other things, whichhas nothing to do with your
team, that has to do withpolitics, with their own
profits, etc, etc. And, then youhave to manage that. That is not
always easy. It's sometimes alsofrustrating. So, why is that not
(16:50):
so important for you, because weare working at something that is
much, much bigger. And if you ifyou can be part of that, what do
you want, more? If you get moreoptions, less or more, I learned
by the hard way that this isabsolutely part of it. And you
have to manage it. You have totake it with you for the better
or the worse. And, that isimportant not to ignore, because
(17:14):
everybody has to go in the samedirection.. That I learned
really, also, that's both forthe managers, as you involve
your collaborators, but also foryour investors, which less often
have the very personal viewsthat you have to communicate
with and to address to keepeverybody in the same boat.
(17:36):
Sometimes you have to managesome silly things.
John Simboli (17:41):
When you're setting out to first build a
company, are there moments whenyou remind members of your team,
this is my dream. I want you tobe part of my dream, but it is
my dream. Is that part of what'srequired to be a leader? Or can
you share that dream? How do youdo that?
Erik Buntinx (17:57):
That's absolutely required. Because if you're
honest, if I'm honest withmyself, I have also other
choices to do other jobs also.
To stay as enthusiastic and asconvinced as much you will have
to own your dream, and you maynot let flaws in your dream, it
may not undermine you yourdream. And sometimes it happens,
(18:19):
not by purpose, but it happensthat there are ideas or ways
that are presented that is notaligned with your dream. And if
you allow that, then, at acertain value, you will realize
this not why why I'm doing this,and that's a dissociation that
can be very dangerous. Soindeed, I must say, I must
(18:42):
emphasize first very, very muchthat almost all people who will
join me, they recognize this isthe dream of Erik. This is his
idea, and we join his idea andthese people are so loyal that
even more than I can say. Butsometimes you have, here and
(19:03):
there, also somebody of which donot expect that was not in that
line and step by step isbringing his own interest, his
own views and so a negative onyour dream. And then you have to
make a hard decision. Then youhave to get rid of that person,
absolutely. Otherwise, it willpoison your own feeling, it will
(19:25):
poison your whole team, yourproject. So I have learned. In
the beginning I was verycautious about that. And if I
think back I allowed too much, Iwas too soft. So in that
respect, harder, yes. When Ifeel that there is somebody who
cannot align with our strategy,with our dynamics, with our
(19:46):
uncertainties, that is also partof the concepts. Then I say,
look, we say better goodbye.
John Simboli (19:58):
Alright, let me shift to the more of a focus on
ANeuroTech and how you'releading it. So is it possible to
say in a very short and conciseway, what the scientific idea is
that you brought to start it up.
What was the realization thatyou had?
Erik Buntinx (20:17):
Yes, so what we know in depression is that
people are treated withantidepressants, that only half
of them are responding well, theother half are responding
somewhat. And then you have toask yourself, what is the reason
behind that? Why is somebodyresponding, let's say 99%, and
(20:39):
another person 30%? And thatbrought me to pharmacology, how
these things work. You have torealize, when I was research,
resident in Maastricht, we onlystarted to know how the brain
was working in relattion toemotions and moods. And realized
that receptors in the brain, sothat are lending points 13 to 2a
(21:03):
dopamine D4, very specificreceptors in the brain, that if
you could organize them at arelative level, that this could
enhance, this could improve theeffect of antidepressants. That
was my thesis, a lot of researchwas done to show that this could
be true. And then was thequestion, I said, can you find a
(21:25):
molecule or synthesize amolecule? The answer on that
last question was potentiallyimpossible? So I got the idea,
there, you see how theentrepreneurial drive is, maybe
there is some compound andnobody knows that it exists.
Then we did further research.
And indeed, we showed that istrue.
John Simboli (21:48):
Do you recall, where you poring through the
literature, were you looking atdata from previous studies? Do
you remember a moment you said,this is the one?
Erik Buntinx (21:58):
Oh, yeah, that's, the so called Aha. Yeah,
absolutely. I got that idea andit was expressed by certain
scientific thresholds. So veryspecific numbers. So you take
these numbers, and then you seewhat the profiling of these
(22:18):
molecules are. And really, Iwent to a whole day to review
all these papers and foundnothing. And then I got that
paper, and the strange thing isthat Dr. Paul Janssen, together
(22:39):
with Josee Leysen, who was atthat time, his right hand in
pharmacology, see is also a verybig, big lady in this field,
they just had published a paperwith data from in vitro/in vivo,
it was a combination. And if youlook at these different
(22:59):
compounds, and if you looked atthis cross very carefully, then
at a certain point, I saw ohPipamperone is just different.
It's just different from allthese. While they had put it in
a whole group, because it wasthe same chemical structure.
They even, themselves, didn'trealize that this was different.
(23:20):
And that was the big aha. Then,oh, how can you then make these
specific qualities of the drugclinically relevant? And I
studied further, and then theidea was if you reduced those,
extremely, that's not by 10,that's by 100, and even 200, and
then maybe it will be soselective in the brain. And that
(23:43):
was my invention. Nobody thoughtabout it. Nobody had used it.
And so that that was theinvention.
John Simboli (23:50):
What that reminds me of is, I can't remember which
founder or scientist who it wasI spoke with, but he said, the
aha moment is not sudden flashof light realization. It was a
"That's funny", as he looked atthe data. "That's funny,
something doesn't quite add uphere. " Was there an aspect of
that was an illumination or wasit? Let me think some more
(24:12):
about? Somthing's not . . . I'vegot to look further here.,"
Erik Buntinx (24:17):
It was both. It was illumination, certainly,
because I saw these figures. Andwhen I saw it, at a certain
moment, you see certain aspectsthat you've never seen. And
then, once you've seen it, youcontinue to see it. But also the
second point, is this really . .
. can that be? Because nobodyhas seen this. This has been
(24:38):
used in a complete other way. Solet's check if that is something
relevant, that can be true in ahuman brain. And so with that, I
went to my IP lawyer, but I alsowent to a good friend who did
imaging studies on dogs. I toldhim I said, yeah, maybe we could
(25:03):
try to show that in a dog. Andso we made a paradigm with that
work. And we treated severaldogs. And we saw, yeah, look,
this is certain to 2Aantagonism. And we see nothing
else. And so the dogs, helped torealize this idea.
John Simboli (25:27):
That's remarkable.
I can't pick another word.
You've taken that idea, you'vetested it out a bit, you've
worked through the imaging withthe dogs, you're ready to go,
you're building this company,then you have to begin to tell
that story, I would think. in away that investors will grasp at
the very beginning. So whenyou're bringing it down to that
really essential part of it? Andthey say, Well, okay, I'm glad
(25:50):
to be here today. Erik, tell mewhat is ANeuroTech, at that
point? What is the answer tothat?
Erik Buntinx (25:57):
Well, I think that's very specific for my
situation that that ideas befounded on my scientific work.
And secondly, also my clinicalwork, because we could use,
already, this work in patientshere in Belgium. And with these
(26:18):
data, I really went to all theseinterested people to show look
this is what I've seen as aclinician. You believe it or
not? And yeah, that's alsoagain, also personal. And you
try to find signals, you adaptbased on your findings, your
concepts that is most feasible,most effective. And that's
(26:41):
that's how we have done it.
John Simboli (26:42):
I think you've addressed this, why didn't
anybody do this before part, butlet me ask the question. So in
those early stages, I'm guessingthat there must have been some
investors who said, this seemsreally interesting, Erik, but if
it's such a good idea, whydidn't anybody do it before? How
did you get that question? Howdid you answer it?
Erik Buntinx (27:01):
I still get this question.. The explanation is,
in fact, scientifically, becausethat's also a coincidence.
Probably, but at the time that Iwas a research affiliate at
Maastricht, the whole of thegoal of monoaminergic theory of
treating depression with allthese neurotransmitters, such as
(27:25):
serotonin, dopamine, was thenvery hot. I had luck, also to
have a project be headed by myprofessor who was, at that
moment, one of the absolutelykey opinion leaders in the world
on that monoaminergicpharmacological thesis. And that
stimulated me, of course, tothink about it. But how the
(27:48):
knowledge about receptors in thebrain, I'm telling you, talking
about 1991 or 1992, was justemerging. And so that plays
down, I developed concepts thatwere just busy with receptor
OOG, selecting receptors fromcells, and then see what are the
(28:10):
affinity that works forreceptors can be a little bit
compared to what happened withthe mRNA, that's also something
that is new, and all of thesudden, it is reality. And so,
let's say I was busy with that.
Other people discovered things,I came to the idea. And this
(28:31):
logic that before that, nobodycame to that because the science
was not there. Nobody knewanything about how receptors
were working. We had no commonknowledge, let's say. You have
to realize that this is onlymore than 25-30 years, not
earlier. Drugs were found by, onthe one hand, chemical
(28:57):
synthesis, and then you treatedanimals with that. And based on
what you saw with animals, yousay, Okay, this is a drug
working for high blood pressure,but you didn't know how it
worked.``
John Simboli (29:12):
I want to ask you more about the mechanism. But
first, let's talk a little bitabout the gap, the gap between
the standard of care that youknew about when you first
developed this idea, and thenhow it's evolved, and then how
what you're trying to do, whatyou're working on, how that
meets that that gap forpatients?
Erik Buntinx (29:31):
Well, honestly, John, it's a sad story, but
that's also the reason why wehave to work very, very hard for
that. The sad story is that,let's say, in the last 30-40
years, no real improvement intreating this devastating
disease such as depression hasbeen realized. There have been
new molecules, there have beennew techniques, but they are
(29:56):
coming at pretty high safetycost. so that people have safety
problems, adverse events, whichfrequently also continue and get
worse the longer you take it. Sothat's not a very attractive
treatment. Or they have a highsafety burden, or they are very
complicated, with a very highlevel threshold. So that's not
(30:20):
accessible, too expensive, andcertainly not in the long term.
So a good solution for patientssuffering from this disease, as
chronic disease, namely, thatyou have an easy to take or easy
to adapt treatment at almost nosafety costs, not clinically
relevant. It's simply not yetthere. And with our a ANT-01,
(30:42):
compound as adjunctivetreatment, we think that we have
that. The data are showing thatyou can treat patients
adjunctively with our compounds,at in fact, no clinical relevant
digital safety burden. And thatonce the patients will get their
response, that response is verysubstantial. In that way we see
(31:04):
that most of these respondersare continuing to take this for
years. In my sample, which Iobserve and treat, the mean
intake is currently 11.1 years.
So this is different from thecurrent and still unsolved
treatment problems in that inthat space.
John Simboli (31:29):
What is the scope in terms of numbers of patients?
And what is the severity? Whatare these patients lives like
now, who have partial orincomplete answers?
Erik Buntinx (31:41):
Well, the main problem is the negative outcome
that we translate in what wecall treatment resistant
depression, TRD. Everybody'stalking about it. Well, you have
to realize nobody starts withTRD. S omebody will get his
first depression, it's not a TRDpatient, he becomes a TRD
(32:03):
patient, because all histreatments that he went through
did not respond sufficiently. Aswith cancer, it's very hard to
say that, if your treatment isnot responding well, you will
end up with your cancer and alsodramatically with that. So that
(32:23):
is what what is very important.
We have to have developedtreatments which prevent the
risk to become a treatmentresistant depression patient.
And that is by having, as quickas possible, treatments
implemented in the patient whichwill bring the patient to full
recovery, brings the patient toa full resolution of all their
(32:45):
symptoms, including what we callresidual symptoms. A lot of
patients who have depressiveepisodes do have residual
symptoms, as they still haveproblems with, for instance,
their level of feeling pleasure.
So they feel not that pleasurefeelings anymore than they had
before the depression. They havealso cognitive problems, they
(33:07):
have not the concentrationcapabilities anymore that they
had before. This is not aconsequence of depression, which
was often thought. No, it isunsolved residual symptoms. And
these residual symptoms, as youcan imagine, are of course, the
basis, the seed, for the newepisode. And so that's the
(33:29):
reason why depressions arecycling. So you have to attack
these problems very efficiently.
And there, I think, we havesomething that, not for
everybody, of course, that wedon't say, but if you have a
drug or treatment, whatever,again for you to resolve the
whole palette of symptoms thatyou're recovered fullly, and you
(33:49):
can continue that treatmentbecause then it protects you
from a relapse at no safetycosts. You have no weight gain,
you have no Parkinsonism youhave no metabolic syndrome, you
have no hypertension, and youcontinue that for your whole
life and it protects you from anew episode. Well, this is
fantastic. Then you preventdepression as a chronic disease.
John Simboli (34:14):
That sounds like the the word that we're all very
careful about not using. Thatsounds like the word cure. Would
you use that word?
Erik Buntinx (34:23):
Absolutely. I think we have to change the
paradigm. As you can imagine,I'm a psychiatrist by training
and people who know me from alsomy, my first years of residency,
I've been called an atypicalpsychiatrist, very
entrepreneurial, dynamic. I wantto get problem solved. I'm not
(34:46):
so big a fan of the care model,I must say. So we have to cure.
For me, it's still shocking howmuch is invested. And that's
okay, I can understand that. I'mnot against it. But it's
shocking that so much isinvested in care, which has to
(35:09):
be, but less in cure. No, wehave to try to help these people
with the cure. That has alwaysdriven me, also, in my own
clinical practice to bringpeople back to their normal
state.
John Simboli (35:25):
Is it possible to talk about what is clinical
depression and how severely itaffects the lives of people
you're trying to treat?
Erik Buntinx (35:33):
I can, I think, start with a very simple
comparison. When we awake, wehave a hunger, we feel energy to
get up to do things that arewhat we call vital elements. And
your mood is also such a vitalphysiological phenomenon. So you
(35:53):
wake up and you feel interest.
You feel some interest inexperiencing doing things,
whatever. A person with clinicaldepression, has lost that vital
mood experience. So when heawakes, he has not a feeling
that something is interesting,that something can give them
pleasure. That the whole day isone big, let's say, burden. They
(36:16):
wake up and they think, Oh, howquickly will the evening come?
And that's the key ofdepression. So in your brain,
similarly, your mood center isjust not clicking on, or it is
clicking on a little bit, andthen going away. And that is not
(36:38):
going to put you on the levelthat you need to experience your
existence as meaningful. And we,as conscious subjects, think
that's the opposite withanimals, and most do not have
clinical depression, that as weare conscious subjects in our
consciousness, we must have alsothat mood experience. So because
(37:03):
you can say to yourself, whenyou wake, is this a day that I
enjoy, or I hope to enjoy? Or isthere the day that I do not
want, you can make that. Sonormally your mood will say this
is the day, a new day for me.
(37:24):
But for a person with clinicaldepression, not the case
For the therapies that you'reworking on now, what specific
anymore. So they lose thefundamental feeling of
meaningfulness, which bringshopelessness, which brings also
suicidal ideas because what whyam I here on this world? What am
I doing? Maybe it would bebetter if I were not walking on
(37:46):
this planet. And that holdstogether with other vital
elements such as appetite, sleeppattern, concentration, all your
system is then taken down. Soyour mood center is something, a
core center that that drivesalso other vital functions. We
(38:09):
know that has to deal with, ofcourse, the brain. We know that
certain regions are involved andcertain pathways are involved.
But we don't have any idea aboutthe cause. The root cause is not
known, although there have beenexecuted massive studies on the
relation between life factors,life events, and depression.
(38:33):
Much of this big research hasbeen able to make any relevant
association between life eventsand depression.
parts of depression are youhoping to address and how many
of those folks are there? Itsounds like depression is not a
one time thing in someone'slife, it may be multiple, How
(38:56):
many and how often and what doyou hope to achieve?
The problem is the incidence. Sothe frequency of depression has
grown enormously in the Westernworld, that at least we know.
And pre-COVID, we were about 8%.
And now post-COVID, we are at12%. So that's enormous. And the
big part of that is also withinyoungsters. Why that is, that's
(39:22):
fairly difficult to explain, butit's very often. You may simply
say that one in 10 persons areconfronted with major depression
at least once in their life butoften repetitively. We see a lot
of know also in the clinic,older people, people of let's
say 65-70-75 which was thoughtrare 20 years ago, but these
(39:46):
people want to have also aquality of life. But it also a
very interesting observation forus is that if you have a medical
history of these patientsaligned and you see that their
current depressive episode isnot a single episode. Then they
say, when I was 21, there was aperiod at 45. And now the third
(40:06):
time. So there is apredisposition, often recurrent.
And I said, before, the periodsbetween one and the other
episodes, mostly are not givinga full resolution. There's
always some baseline of somedepressed feelings here.
John Simboli (40:27):
That's very helpful. This is a bit of a
jump, but let's talk about themechanism of action. So how do
your drug candidates work? Whatis the mechanism of action?
Erik Buntinx (40:37):
That fundamentally stays with what we call the
monoaminergic hypothesis. Thatmeans we have a group of
chemical entities that we callthe monoamines. And these
chemical entities are mainly inthe brain playing between the
neurons—serotonin, dopamine,noradrenalin, are very typical
(40:59):
chemical entities, in fact. Andyou must see this as a kind of
messenger. They are produced bythe cells. And they are then
transported from the one cell,one neuron to the other neuron,
to give a message or messages.
And so the brain is talking withitself. And that communication
scheme is, in my opinion,disturbed in patients suffering
(41:21):
from depression. And by havingsome influence on that talking
system, by enhancing theserotonin, by reducing some
receptors that are responding onthese neurotransmitters. So you
regulate a little bit, andthat's little bit trial and
(41:41):
error. But regulating thecommunication system can bring
back the normal moodsmanagement. It's a little bit
like, let's imagine that youhave your cell phone, and some
apps are not working, becausethere's a bug in it. There is
something wrong withcommunication. And your IT guys
says, reset. Well, it works. Yousay, how is that possible?
John Simboli (42:05):
Would it be accurate to say you're not
trying to change the chemistryin the body? You're trying to
bring it to its natural state?
Erik Buntinx (42:14):
Yeah, absolutely.
You're not trying to change it,you're trying to improve their
natural working. You're tryingto bring back the normal
communication strategies, sothat they can do their job like
they have done before. It's arestoration effect. And
sometimes you must support thatcontinuously to make sure that
(42:35):
the system is working normally.
That's something that I think wedo as human beings, and even
animals are doing that all day.
I mean, you're wash yourselfrepeatedly not to get some bad
things on your skin. So you'resupporting your system, so that
it can function well. Andthat's, I think, how you could
(42:58):
adress depression. There areother therapies, of course. They
are more what we call invasive,and are bringing in what we
could say, not naturalisticeffects, effects that you would
normally not have. I don't thinkthat that is a solution, I think
that they can give an effect,that's a kind of induced effect.
(43:20):
But it will be very surprising,if you do that, that you will
get a sustained effect. If youdo something which is not common
in nature, mostly, it's notsustainable, I mean, then you
can get counter-actions innature. And these
counter-actions will lead at theend of the day to a kind of
(43:41):
neutralization of your inducedeffects.
John Simboli (43:46):
As you look at where the future of treatment
for depression may go, and whereyour talents may alter how
things are done now, how wouldyou like to change the direction
of where things are going?
Erik Buntinx (43:59):
I think we have to go together for being more
ambitious in taking mentaldiseases very seriously, as an
integral part of our humanbeing. It's not a separate part,
it's not a strange part, it'snot a part that is for some
people. In previous times, weput them in some Institutes. No,
(44:20):
it's everywhere. So the focus oftreating that and resolving that
must be also everywhere. Andthen we go forward with with our
human being. What has driven mealways is, as you mentioned, is
getting results. I want torealize something that is
meaningful and that gives memeaning for my life. I have some
(44:43):
some talents, I got them, theywere given to me by nature, and
I could not accept from myselfthat I would not use them and I
would not try to do somethingmeaningful with them. That's for
me a very important issue.
That's another question, I'mworking very hard and now 61. I
can stop working. And a lot ofpeople say to me, why are you
(45:06):
working so hard, Erik? You'reold. I say this is my life. I
cannot spoil my time for thingsat no meanin. That's really,
really true.
John Simboli (45:20):
Erik, thanks for speaking with me today.
Erik Buntinx (45:22):
Thank you so much, John.
Today I'm speaking with Erik Buntinx, founding CEO
(00:03):
of ANeuroTech, headquartered inAlken, Belgium. Welcome to
BioBoss. Erik.
Erik Buntinx (00:09):
Many thanks, John, to give me the floor. We hope to
have a very interestingconversation.
John Simboli (00:13):
What led to your role as founding CEO of
ANeuroTech?
Erik Buntinx (00:18):
Well, John, I'm very happy with your question
because this is a very personalstory. So my role as founding
CEO is something that came like. . . I was a clinician,
already in my residence years inLeuven, Maastricht years,
studying on depression. Idetected some new mechanisms
that could improve theantidepressant effect in
(00:40):
treating patients. And based onthat concept, I went to some
very well known people such asDr. Paul Janssen, founder of
Janssen Pharmaceutica, toexplain my idea and he was so
enthusiastic that he allowed meto go into his library on all of
these molecules that hesynthesized. And I looked into
(01:02):
that library, I see myself stillsitting in that small room with
all these papers, and all thesebooklets and looking for a
compound that corresponds tothat pharmacological idea and
just found one. And that's thestarting point of being a
founding CEO. I found thatcompound, I could file a patent
(01:24):
on it. And I founded, then, myfirst biotech company, where we
developed that drug in relationto treating depression. I
started with science, withclinical concepts. And went into
the business, raising money.
I've raised, up to date, morethan 25 million euro. And my
board was then asking me, Erik,what do you think about becoming
(01:47):
a CEO? I said, I'm a scientist.
similarly, This was really notrealistic. I mean, coming from
myself and confirmed by others.
But just before I went into thatrole, I got pretty sick. And I
(02:09):
said to these guys, at my board,look, this will not work because
I have to undergo a very seriousoperation. And they say "No, no
problem, Erik when you're readyother coming out of the clinic,
you're welcome." And I went outof the clinic with still some
tubes in me and I see myself atthe first board meeting, where I
was unconfirmed as CEO. Sothat's a little bit of my story
(02:34):
on that.
John Simboli (02:38):
Do you recall, when you had your meeting with
Dr. Janssen, that must have beendear to his heart, because your
research apparently was verymuch something he'd been working
on, something he was interestedin. What did he think when you
came in to talk to him?
Erik Buntinx (02:53):
You have to know I was introduced to him by a very
good friend of mine, which wasDr. Paul Stoffels. He became
afterwards head of R&D atJanssen. And this friend studied
together with me, and he said,"Look, you have to talk with
Paul." And I thought, I willexplain to him the idea and then
Paul can take that forward inhis R&D environment. That was
(03:17):
the idea. So I was very humbledto go to tell something, but
Paul was listening. And healways has been somebody who is
intrigued by "Where's the value?
What is here to make a success?"And his reaction after my
explanation was, "Oh, EriK, Iwill not do that. You have to do
that. That's your drug. And youhave to build a company on
(03:37):
that." I never thought aboutthat. But he said "You have to
go back home. Talk with yourwife, and tell the story." This
was so convincing, that fromthat moment on there was only
one objective and that's mebuilding a company, becoming,
also the founder and the CEO,And he has always supported me
(03:59):
and that's respected.
John Simboli (04:03):
It sounds like as high a compliment, as one could
pay to you to say this hasmerit, go build it. On the other
hand, it was probably dauntingto be confronted all of a sudden
with this idea (04:14):
Oh, I've got to do this.
Erik Buntinx (04:16):
Yes, indeed. And I was wondering why he replied
like that to me. I learned fromPaul, I discussed further with
him. And he explained me to methat when you do this research
work and also this business,what is absolutely key is that
John Simboli (04:32):
Let me ask you about the evolution from
the person, the guy, who mostbelieves it, he has to do it,
because that belief will playdown in the realization and the
success. I think he thought,this we may not take away from
him, from Erik, he's theinventor, he has seen this. He
(04:53):
is a clinician, he knows theins and outs, he has tried this
already in his clinic. So heknows all about it. So that is
the treasure that you have toexplore. Because in biotech and
developing drugs or treatmentsin patients, this is not only
mathematics, it's not a kind ofcalculation. It's a dynamic
(05:18):
process where you have tobalance everything. And to
appreciate what is important,what's not important. And that
brings your product further.
scientist to entrepreneur tobuilding a company to trying to
(05:38):
bring therapeutics to patients.
So at what point did you realizethat you had the entrepreneurial
determination or energy to wantto go out and suggest to
someone, "Hey, I have an ideahere?"
Erik Buntinx (05:51):
I must say this was appealing to own background,
personal background. So alreadyas a child, I was somebody who
was very, very driven with,let's say, a kind of explorer
attitude. And when I was eight,I think a teacher asked me,
"What do you want to be in yourlife?" I said "An astronaut, of
(06:12):
course, I want to explorespace." And I want to go for
these endeavors. And also, as anexample, while I was 12, I was
interested in astronomy, andthen I went to my parents, who
didn't know anything aboutscience. They were farmers, in
fact. And I say, I want to buy atelescope. They're really
(06:36):
shocked. So Oh, my God, what ishappening here? I was driven by
science, but entrepreneurship,doing something, building
something up. So always tryingto realize things. So that is
still in my blood, I think. Andthen you go for medicine
studies, which is not reallyentrepreneurial oriented, of
(06:59):
course, it's more about gettingknowledge, know-how, training,
clinical work, academic work,which I did. So I was then a
little bit away from myentrepreneurial drive. However,
it was always playing in myhead, in my background. And
that's also the reason why Ihave not become, finally, an
academic. I was a researchfellow at University of
(07:22):
Maastricht, where I indeeddiscovered my hypothesis, and
the foundations of ANeuroTechhas been there. But that was
pretty successful. I mean, thatresearch work, and the
professors proposed for me tobecome an academic, and to go
for a chair. And it was yes,it's very attractive. I was in
(07:43):
residence then,, but this wasnot aligned with my personality.
And I had a very good friend,who was pretty much older, I
think, 15 years older than me,he was, in fact, my insurance
agent. I have good contact withhim. He was also admiring what I
was doing. And I asked him, Whatdo you think about it? "Oh, no,
(08:05):
it's very clear, he said, Younever may be become an academic.
You will be unhappy all yourlife." And I explained to him
about my ideas, of course. Andhe said, "Yeah, that's your
way." And really, I took that. Isaid, Look, that's clear. There
is no reason why he would adviseme, without reason. And so I
(08:30):
went for my privateendorsements, I founded my own
outpatient clinic where bigclinical research center was
integrated. So we are currentlydoing very many clinical trials,
sponsored. We are one of thebiggest privately owned clinical
research centers in Europe. Andwithin that framework, I
developed, further, myhypothesis. I discovered that
(08:52):
work, with Janssen, I broughtthat into my research center, we
did further research so that wecould develop IP and so on. So
you see, this is a veryentrepreneurial background,
mentality. And I think I got itfrom my parents. They were
farmers and you know, a farmeris in fact, a real basic
(09:13):
entrepreneur. You have to workon your field, on your animals,
every day. Look what you can dokwhat you can do better.
Otherwise, you will you will godown and this is a dynamic. I
cannot miss.
John Simboli (09:25):
I never thought of it quite like that. There's no
guarantee to being a farmer,right?
Erik Buntinx (09:29):
There's also another story on that because
when I was around 14, my fatheralso tried to do new things. I
don't know how it wasn't in theU.S.,but here in Europe in this
year, we are talking about75-76, strawberries were coming
(09:49):
up as delicacy. And my fatherthought, maybe we have to do
that and I joined him and nobodydid that. We built up a
strawberry farming business thatdid very well. And I did that
with him for four years.
John Simboli (10:08):
Yes, that's an entrepreneurial background. It's
interesting. If we went back towhere you were just a moment
ago, and if your friend who'syour insurance agent, were here
and I said to him, "What was itabout Erik's personality that
made you know, right away, no,this is this is what I see."
(10:30):
What would he say? Whatcharacteristics do you think he
saw in you at that time?
Erik Buntinx (10:35):
That I'm always driven by my ideas, and that I'm
a happy man when I can work onmy ideas, that's for sure. And
that I will be unhappy when Ihave to work on ideas from
others.
John Simboli (10:49):
So you're having a conversation with Dr. Janssen,
and, he said, in effect, itsounds like, this is an
interesting idea, time for youto go home and talk with your
wife and and break the bad newsthat you're going to start a new
company. Do you remember whatthat was like? Was that an okay,
part of your development andyour growth? It's not an easy
thing to do? I wouldn't think.
Erik Buntinx (11:11):
At first, I had the feeling I'm here in a
fantasy, because you have toknow I didn't have any
experience in the form ofbusiness, at all. I didn't know
really what a pharmaceuticalcompany was. I didn't know
anything about raising money,private equity, all of these
things. And there is then thebig Dr. Paul Janssen, who is
(11:34):
absolutely a hero in the world,who is then saying, to me, and I
didn't know him. That was thefirst time I met him. Erik, you
have to go for your own pharmacompany. I came home, I'd said,
Look, maybe this is somethingmad. What is this, an illusion?.
(11:55):
So I had to digest it. Luckily,I was had a good friend, Paul
Stoffels, who knows ins andouts, of course already then,
and other persons we are stillwith me, all these guys said,
yeah, you have to do it. Andeven better, we will join you,
we will support you. So yes,really interesting. And so just
(12:21):
you have to know the situationthat I'm the CEO of a group,
leading a group of people whohave extremely in-depth
experience as experts in thisfield. While I'm coming, in
fact, from a kind of naiveposition. Step by step, I
realized that then I was advisedby my friends to go to an IP
(12:44):
lawyer. I've never heard aboutan IP lawyer. I just went to the
clerk, which is still my IPlawyer, and I said, "Look, I
have to tell a story." And Itold the story. And the first
question, "I will ask you onequestion. Have you ever told
anybody about this?" No. Only myfriends." "Then we are okay,
(13:07):
then we will follow the path".
And yes,, for my personalenvironmental, my wife, etc. My
wife has known me from when wewere 17. So that's, I think,
also very important. And alreadythen, as I told, I was very
entrepreneurial, I did thingsother kids didn't do. I owned my
money, et cetera. So of course,it was a shock for her but it
(13:32):
was also not surprising, at all.
John Simboli (13:37):
As I hear you tell the story I picture two words
that are very similar butthey're very different. So dream
and dreamer. To have a dream,can be a creative act. And it
helps people accomplish thingsthey couldn't even imagine. To
be a dreamer, we think ofsomeone who may never accomplish
those things. Maybe that'sunfair to make it be that
(13:58):
simplistic. But did you know youhad a dream? Did you know you
were not a dreamer?
Erik Buntinx (14:05):
Yes, the dream, of course, of being able to bring
medicine to patients sufferingfrom depression, and that's very
personal because in my familyfrom the mother's side, we had a
lot of people suffering veryheavily from depression,
including suicide. So I wasalready focused on that. But
then thinking that you couldbring a treatment to all these
(14:28):
suffering patients that you havediscovered. Yes,, that's that's
a legacy that give your lifemore worth I think, that's
certainly, absolutely the dream.
But no, I'm not a dreamer. I'malso not a romantic and I think
that's the difference. I have adream, or several dreams, let's
say, but immediately I try tocheck. How can you realize that?
(14:49):
What do you have to do inreality? How does the world work
or the systems work to getsomething done? So, very focused
on these kind of logisticbusiness related concepts. And
that's, I think, an opposite toa dreamer, because a dreamer
doesn't want to do that realitycheck, because then the dream
(15:12):
gets less attractive.
John Simboli (15:18):
When you were negotiating, or maybe that's not
the right word, when you wereworking through that mixture of
creative spark, and idea andrealizing that the next step was
to build something, you probablyhad a pretty good idea as a
logical, rational, scientificmind, what it was that needed to
(15:38):
be done to begin the process ofbuilding a company. But the CEOs
I've spoken with many of themwho are founders, also would
have said to me on BioBoss, as afirst-time CEO I didn't know
what I didn't know, that sort ofthing. So when you pictured what
it would be like, in the verybeginning, first few weeks,
first few months of building acompany, what was that picture?
(16:00):
And then what was that reality?
What was the difference orsimilarity?
Erik Buntinx (16:05):
Why, indeed, starting from this dream, and
you think, yeah, once I canconvince people to invest in it,
and to join also the team, thatthey join your dream, and that
they go on with that story. But,of course, people are people.
And what you then see is thatonce they are there, and sitting
(16:27):
at your board, for instance arein your team, then they are also
popping up other things, whichhas nothing to do with your
team, that has to do withpolitics, with their own
profits, etc, etc. And, then youhave to manage that. That is not
always easy. It's sometimes alsofrustrating. So, why is that not
(16:50):
so important for you, because weare working at something that is
much, much bigger. And if you ifyou can be part of that, what do
you want, more? If you get moreoptions, less or more, I learned
by the hard way that this isabsolutely part of it. And you
have to manage it. You have totake it with you for the better
or the worse. And, that isimportant not to ignore, because
(17:14):
everybody has to go in the samedirection.. That I learned
really, also, that's both forthe managers, as you involve
your collaborators, but also foryour investors, which less often
have the very personal viewsthat you have to communicate
with and to address to keepeverybody in the same boat.
(17:36):
Sometimes you have to managesome silly things.
John Simboli (17:41):
When you're setting out to first build a
company, are there moments whenyou remind members of your team,
this is my dream. I want you tobe part of my dream, but it is
my dream. Is that part of what'srequired to be a leader? Or can
you share that dream? How do youdo that?
Erik Buntinx (17:57):
That's absolutely required. Because if you're
honest, if I'm honest withmyself, I have also other
choices to do other jobs also.
To stay as enthusiastic and asconvinced as much you will have
to own your dream, and you maynot let flaws in your dream, it
may not undermine you yourdream. And sometimes it happens,
(18:19):
not by purpose, but it happensthat there are ideas or ways
that are presented that is notaligned with your dream. And if
you allow that, then, at acertain value, you will realize
this not why why I'm doing this,and that's a dissociation that
can be very dangerous. Soindeed, I must say, I must
(18:42):
emphasize first very, very muchthat almost all people who will
join me, they recognize this isthe dream of Erik. This is his
idea, and we join his idea andthese people are so loyal that
even more than I can say. Butsometimes you have, here and
(19:03):
there, also somebody of which donot expect that was not in that
line and step by step isbringing his own interest, his
own views and so a negative onyour dream. And then you have to
make a hard decision. Then youhave to get rid of that person,
absolutely. Otherwise, it willpoison your own feeling, it will
(19:25):
poison your whole team, yourproject. So I have learned. In
the beginning I was verycautious about that. And if I
think back I allowed too much, Iwas too soft. So in that
respect, harder, yes. When Ifeel that there is somebody who
cannot align with our strategy,with our dynamics, with our
(19:46):
uncertainties, that is also partof the concepts. Then I say,
look, we say better goodbye.
John Simboli (19:58):
Alright, let me shift to the more of a focus on
ANeuroTech and how you'releading it. So is it possible to
say in a very short and conciseway, what the scientific idea is
that you brought to start it up.
What was the realization thatyou had?
Erik Buntinx (20:17):
Yes, so what we know in depression is that
people are treated withantidepressants, that only half
of them are responding well, theother half are responding
somewhat. And then you have toask yourself, what is the reason
behind that? Why is somebodyresponding, let's say 99%, and
(20:39):
another person 30%? And thatbrought me to pharmacology, how
these things work. You have torealize, when I was research,
resident in Maastricht, we onlystarted to know how the brain
was working in relattion toemotions and moods. And realized
that receptors in the brain, sothat are lending points 13 to 2a
(21:03):
dopamine D4, very specificreceptors in the brain, that if
you could organize them at arelative level, that this could
enhance, this could improve theeffect of antidepressants. That
was my thesis, a lot of researchwas done to show that this could
be true. And then was thequestion, I said, can you find a
(21:25):
molecule or synthesize amolecule? The answer on that
last question was potentiallyimpossible? So I got the idea,
there, you see how theentrepreneurial drive is, maybe
there is some compound andnobody knows that it exists.
Then we did further research.
And indeed, we showed that istrue.
John Simboli (21:48):
Do you recall, where you poring through the
literature, were you looking atdata from previous studies? Do
you remember a moment you said,this is the one?
Erik Buntinx (21:58):
Oh, yeah, that's, the so called Aha. Yeah,
absolutely. I got that idea andit was expressed by certain
scientific thresholds. So veryspecific numbers. So you take
these numbers, and then you seewhat the profiling of these
(22:18):
molecules are. And really, Iwent to a whole day to review
all these papers and foundnothing. And then I got that
paper, and the strange thing isthat Dr. Paul Janssen, together
(22:39):
with Josee Leysen, who was atthat time, his right hand in
pharmacology, see is also a verybig, big lady in this field,
they just had published a paperwith data from in vitro/in vivo,
it was a combination. And if youlook at these different
(22:59):
compounds, and if you looked atthis cross very carefully, then
at a certain point, I saw ohPipamperone is just different.
It's just different from allthese. While they had put it in
a whole group, because it wasthe same chemical structure.
They even, themselves, didn'trealize that this was different.
(23:20):
And that was the big aha. Then,oh, how can you then make these
specific qualities of the drugclinically relevant? And I
studied further, and then theidea was if you reduced those,
extremely, that's not by 10,that's by 100, and even 200, and
then maybe it will be soselective in the brain. And that
(23:43):
was my invention. Nobody thoughtabout it. Nobody had used it.
And so that that was theinvention.
John Simboli (23:50):
What that reminds me of is, I can't remember which
founder or scientist who it wasI spoke with, but he said, the
aha moment is not sudden flashof light realization. It was a
"That's funny", as he looked atthe data. "That's funny,
something doesn't quite add uphere. " Was there an aspect of
that was an illumination or wasit? Let me think some more
(24:12):
about? Somthing's not . . . I'vegot to look further here.,"
Erik Buntinx (24:17):
It was both. It was illumination, certainly,
because I saw these figures. Andwhen I saw it, at a certain
moment, you see certain aspectsthat you've never seen. And
then, once you've seen it, youcontinue to see it. But also the
second point, is this really . .
. can that be? Because nobodyhas seen this. This has been
(24:38):
used in a complete other way. Solet's check if that is something
relevant, that can be true in ahuman brain. And so with that, I
went to my IP lawyer, but I alsowent to a good friend who did
imaging studies on dogs. I toldhim I said, yeah, maybe we could
(25:03):
try to show that in a dog. Andso we made a paradigm with that
work. And we treated severaldogs. And we saw, yeah, look,
this is certain to 2Aantagonism. And we see nothing
else. And so the dogs, helped torealize this idea.
John Simboli (25:27):
That's remarkable.
I can't pick another word.
You've taken that idea, you'vetested it out a bit, you've
worked through the imaging withthe dogs, you're ready to go,
you're building this company,then you have to begin to tell
that story, I would think. in away that investors will grasp at
the very beginning. So whenyou're bringing it down to that
really essential part of it? Andthey say, Well, okay, I'm glad
(25:50):
to be here today. Erik, tell mewhat is ANeuroTech, at that
point? What is the answer tothat?
Erik Buntinx (25:57):
Well, I think that's very specific for my
situation that that ideas befounded on my scientific work.
And secondly, also my clinicalwork, because we could use,
already, this work in patientshere in Belgium. And with these
(26:18):
data, I really went to all theseinterested people to show look
this is what I've seen as aclinician. You believe it or
not? And yeah, that's alsoagain, also personal. And you
try to find signals, you adaptbased on your findings, your
concepts that is most feasible,most effective. And that's
(26:41):
that's how we have done it.
John Simboli (26:42):
I think you've addressed this, why didn't
anybody do this before part, butlet me ask the question. So in
those early stages, I'm guessingthat there must have been some
investors who said, this seemsreally interesting, Erik, but if
it's such a good idea, whydidn't anybody do it before? How
did you get that question? Howdid you answer it?
Erik Buntinx (27:01):
I still get this question.. The explanation is,
in fact, scientifically, becausethat's also a coincidence.
Probably, but at the time that Iwas a research affiliate at
Maastricht, the whole of thegoal of monoaminergic theory of
treating depression with allthese neurotransmitters, such as
(27:25):
serotonin, dopamine, was thenvery hot. I had luck, also to
have a project be headed by myprofessor who was, at that
moment, one of the absolutelykey opinion leaders in the world
on that monoaminergicpharmacological thesis. And that
stimulated me, of course, tothink about it. But how the
(27:48):
knowledge about receptors in thebrain, I'm telling you, talking
about 1991 or 1992, was justemerging. And so that plays
down, I developed concepts thatwere just busy with receptor
OOG, selecting receptors fromcells, and then see what are the
(28:10):
affinity that works forreceptors can be a little bit
compared to what happened withthe mRNA, that's also something
that is new, and all of thesudden, it is reality. And so,
let's say I was busy with that.
Other people discovered things,I came to the idea. And this
(28:31):
logic that before that, nobodycame to that because the science
was not there. Nobody knewanything about how receptors
were working. We had no commonknowledge, let's say. You have
to realize that this is onlymore than 25-30 years, not
earlier. Drugs were found by, onthe one hand, chemical
(28:57):
synthesis, and then you treatedanimals with that. And based on
what you saw with animals, yousay, Okay, this is a drug
working for high blood pressure,but you didn't know how it
worked.``
John Simboli (29:12):
I want to ask you more about the mechanism. But
first, let's talk a little bitabout the gap, the gap between
the standard of care that youknew about when you first
developed this idea, and thenhow it's evolved, and then how
what you're trying to do, whatyou're working on, how that
meets that that gap forpatients?
Erik Buntinx (29:31):
Well, honestly, John, it's a sad story, but
that's also the reason why wehave to work very, very hard for
that. The sad story is that,let's say, in the last 30-40
years, no real improvement intreating this devastating
disease such as depression hasbeen realized. There have been
new molecules, there have beennew techniques, but they are
(29:56):
coming at pretty high safetycost. so that people have safety
problems, adverse events, whichfrequently also continue and get
worse the longer you take it. Sothat's not a very attractive
treatment. Or they have a highsafety burden, or they are very
complicated, with a very highlevel threshold. So that's not
(30:20):
accessible, too expensive, andcertainly not in the long term.
So a good solution for patientssuffering from this disease, as
chronic disease, namely, thatyou have an easy to take or easy
to adapt treatment at almost nosafety costs, not clinically
relevant. It's simply not yetthere. And with our a ANT-01,
(30:42):
compound as adjunctivetreatment, we think that we have
that. The data are showing thatyou can treat patients
adjunctively with our compounds,at in fact, no clinical relevant
digital safety burden. And thatonce the patients will get their
response, that response is verysubstantial. In that way we see
(31:04):
that most of these respondersare continuing to take this for
years. In my sample, which Iobserve and treat, the mean
intake is currently 11.1 years.
So this is different from thecurrent and still unsolved
treatment problems in that inthat space.
John Simboli (31:29):
What is the scope in terms of numbers of patients?
And what is the severity? Whatare these patients lives like
now, who have partial orincomplete answers?
Erik Buntinx (31:41):
Well, the main problem is the negative outcome
that we translate in what wecall treatment resistant
depression, TRD. Everybody'stalking about it. Well, you have
to realize nobody starts withTRD. S omebody will get his
first depression, it's not a TRDpatient, he becomes a TRD
(32:03):
patient, because all histreatments that he went through
did not respond sufficiently. Aswith cancer, it's very hard to
say that, if your treatment isnot responding well, you will
end up with your cancer and alsodramatically with that. So that
(32:23):
is what what is very important.
We have to have developedtreatments which prevent the
risk to become a treatmentresistant depression patient.
And that is by having, as quickas possible, treatments
implemented in the patient whichwill bring the patient to full
recovery, brings the patient toa full resolution of all their
(32:45):
symptoms, including what we callresidual symptoms. A lot of
patients who have depressiveepisodes do have residual
symptoms, as they still haveproblems with, for instance,
their level of feeling pleasure.
So they feel not that pleasurefeelings anymore than they had
before the depression. They havealso cognitive problems, they
(33:07):
have not the concentrationcapabilities anymore that they
had before. This is not aconsequence of depression, which
was often thought. No, it isunsolved residual symptoms. And
these residual symptoms, as youcan imagine, are of course, the
basis, the seed, for the newepisode. And so that's the
(33:29):
reason why depressions arecycling. So you have to attack
these problems very efficiently.
And there, I think, we havesomething that, not for
everybody, of course, that wedon't say, but if you have a
drug or treatment, whatever,again for you to resolve the
whole palette of symptoms thatyou're recovered fullly, and you
(33:49):
can continue that treatmentbecause then it protects you
from a relapse at no safetycosts. You have no weight gain,
you have no Parkinsonism youhave no metabolic syndrome, you
have no hypertension, and youcontinue that for your whole
life and it protects you from anew episode. Well, this is
fantastic. Then you preventdepression as a chronic disease.
John Simboli (34:14):
That sounds like the the word that we're all very
careful about not using. Thatsounds like the word cure. Would
you use that word?
Erik Buntinx (34:23):
Absolutely. I think we have to change the
paradigm. As you can imagine,I'm a psychiatrist by training
and people who know me from alsomy, my first years of residency,
I've been called an atypicalpsychiatrist, very
entrepreneurial, dynamic. I wantto get problem solved. I'm not
(34:46):
so big a fan of the care model,I must say. So we have to cure.
For me, it's still shocking howmuch is invested. And that's
okay, I can understand that. I'mnot against it. But it's
shocking that so much isinvested in care, which has to
(35:09):
be, but less in cure. No, wehave to try to help these people
with the cure. That has alwaysdriven me, also, in my own
clinical practice to bringpeople back to their normal
state.
John Simboli (35:25):
Is it possible to talk about what is clinical
depression and how severely itaffects the lives of people
you're trying to treat?
Erik Buntinx (35:33):
I can, I think, start with a very simple
comparison. When we awake, wehave a hunger, we feel energy to
get up to do things that arewhat we call vital elements. And
your mood is also such a vitalphysiological phenomenon. So you
(35:53):
wake up and you feel interest.
You feel some interest inexperiencing doing things,
whatever. A person with clinicaldepression, has lost that vital
mood experience. So when heawakes, he has not a feeling
that something is interesting,that something can give them
pleasure. That the whole day isone big, let's say, burden. They
(36:16):
wake up and they think, Oh, howquickly will the evening come?
And that's the key ofdepression. So in your brain,
similarly, your mood center isjust not clicking on, or it is
clicking on a little bit, andthen going away. And that is not
(36:38):
going to put you on the levelthat you need to experience your
existence as meaningful. And we,as conscious subjects, think
that's the opposite withanimals, and most do not have
clinical depression, that as weare conscious subjects in our
consciousness, we must have alsothat mood experience. So because
(37:03):
you can say to yourself, whenyou wake, is this a day that I
enjoy, or I hope to enjoy? Or isthere the day that I do not
want, you can make that. Sonormally your mood will say this
is the day, a new day for me.
(37:24):
But for a person with clinicaldepression, not the case
For the therapies that you'reworking on now, what specific
anymore. So they lose thefundamental feeling of
meaningfulness, which bringshopelessness, which brings also
suicidal ideas because what whyam I here on this world? What am
I doing? Maybe it would bebetter if I were not walking on
(37:46):
this planet. And that holdstogether with other vital
elements such as appetite, sleeppattern, concentration, all your
system is then taken down. Soyour mood center is something, a
core center that that drivesalso other vital functions. We
(38:09):
know that has to deal with, ofcourse, the brain. We know that
certain regions are involved andcertain pathways are involved.
But we don't have any idea aboutthe cause. The root cause is not
known, although there have beenexecuted massive studies on the
relation between life factors,life events, and depression.
(38:33):
Much of this big research hasbeen able to make any relevant
association between life eventsand depression.
parts of depression are youhoping to address and how many
of those folks are there? Itsounds like depression is not a
one time thing in someone'slife, it may be multiple, How
(38:56):
many and how often and what doyou hope to achieve?
The problem is the incidence. Sothe frequency of depression has
grown enormously in the Westernworld, that at least we know.
And pre-COVID, we were about 8%.
And now post-COVID, we are at12%. So that's enormous. And the
big part of that is also withinyoungsters. Why that is, that's
(39:22):
fairly difficult to explain, butit's very often. You may simply
say that one in 10 persons areconfronted with major depression
at least once in their life butoften repetitively. We see a lot
of know also in the clinic,older people, people of let's
say 65-70-75 which was thoughtrare 20 years ago, but these
(39:46):
people want to have also aquality of life. But it also a
very interesting observation forus is that if you have a medical
history of these patientsaligned and you see that their
current depressive episode isnot a single episode. Then they
say, when I was 21, there was aperiod at 45. And now the third
(40:06):
time. So there is apredisposition, often recurrent.
And I said, before, the periodsbetween one and the other
episodes, mostly are not givinga full resolution. There's
always some baseline of somedepressed feelings here.
John Simboli (40:27):
That's very helpful. This is a bit of a
jump, but let's talk about themechanism of action. So how do
your drug candidates work? Whatis the mechanism of action?
Erik Buntinx (40:37):
That fundamentally stays with what we call the
monoaminergic hypothesis. Thatmeans we have a group of
chemical entities that we callthe monoamines. And these
chemical entities are mainly inthe brain playing between the
neurons—serotonin, dopamine,noradrenalin, are very typical
(40:59):
chemical entities, in fact. Andyou must see this as a kind of
messenger. They are produced bythe cells. And they are then
transported from the one cell,one neuron to the other neuron,
to give a message or messages.
And so the brain is talking withitself. And that communication
scheme is, in my opinion,disturbed in patients suffering
(41:21):
from depression. And by havingsome influence on that talking
system, by enhancing theserotonin, by reducing some
receptors that are responding onthese neurotransmitters. So you
regulate a little bit, andthat's little bit trial and
(41:41):
error. But regulating thecommunication system can bring
back the normal moodsmanagement. It's a little bit
like, let's imagine that youhave your cell phone, and some
apps are not working, becausethere's a bug in it. There is
something wrong withcommunication. And your IT guys
says, reset. Well, it works. Yousay, how is that possible?
John Simboli (42:05):
Would it be accurate to say you're not
trying to change the chemistryin the body? You're trying to
bring it to its natural state?
Erik Buntinx (42:14):
Yeah, absolutely.
You're not trying to change it,you're trying to improve their
natural working. You're tryingto bring back the normal
communication strategies, sothat they can do their job like
they have done before. It's arestoration effect. And
sometimes you must support thatcontinuously to make sure that
(42:35):
the system is working normally.
That's something that I think wedo as human beings, and even
animals are doing that all day.
I mean, you're wash yourselfrepeatedly not to get some bad
things on your skin. So you'resupporting your system, so that
it can function well. Andthat's, I think, how you could
(42:58):
adress depression. There areother therapies, of course. They
are more what we call invasive,and are bringing in what we
could say, not naturalisticeffects, effects that you would
normally not have. I don't thinkthat that is a solution, I think
that they can give an effect,that's a kind of induced effect.
(43:20):
But it will be very surprising,if you do that, that you will
get a sustained effect. If youdo something which is not common
in nature, mostly, it's notsustainable, I mean, then you
can get counter-actions innature. And these
counter-actions will lead at theend of the day to a kind of
(43:41):
neutralization of your inducedeffects.
John Simboli (43:46):
As you look at where the future of treatment
for depression may go, and whereyour talents may alter how
things are done now, how wouldyou like to change the direction
of where things are going?
Erik Buntinx (43:59):
I think we have to go together for being more
ambitious in taking mentaldiseases very seriously, as an
integral part of our humanbeing. It's not a separate part,
it's not a strange part, it'snot a part that is for some
people. In previous times, weput them in some Institutes. No,
(44:20):
it's everywhere. So the focus oftreating that and resolving that
must be also everywhere. Andthen we go forward with with our
human being. What has driven mealways is, as you mentioned, is
getting results. I want torealize something that is
meaningful and that gives memeaning for my life. I have some
(44:43):
some talents, I got them, theywere given to me by nature, and
I could not accept from myselfthat I would not use them and I
would not try to do somethingmeaningful with them. That's for
me a very important issue.
That's another question, I'mworking very hard and now 61. I
can stop working. And a lot ofpeople say to me, why are you
(45:06):
working so hard, Erik? You'reold. I say this is my life. I
cannot spoil my time for thingsat no meanin. That's really,
really true.
John Simboli (45:20):
Erik, thanks for speaking with me today.
Erik Buntinx (45:22):
Thank you so much, John.
Popular Podcasts
On Purpose with Jay Shetty
I’m Jay Shetty host of On Purpose the worlds #1 Mental Health podcast and I’m so grateful you found us. I started this podcast 5 years ago to invite you into conversations and workshops that are designed to help make you happier, healthier and more healed. I believe that when you (yes you) feel seen, heard and understood you’re able to deal with relationship struggles, work challenges and life’s ups and downs with more ease and grace. I interview experts, celebrities, thought leaders and athletes so that we can grow our mindset, build better habits and uncover a side of them we’ve never seen before. New episodes every Monday and Friday. Your support means the world to me and I don’t take it for granted — click the follow button and leave a review to help us spread the love with On Purpose. I can’t wait for you to listen to your first or 500th episode!
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.
Ridiculous History
History is beautiful, brutal and, often, ridiculous. Join Ben Bowlin and Noel Brown as they dive into some of the weirdest stories from across the span of human civilization in Ridiculous History, a podcast by iHeartRadio.