July 23, 2025 • 23 mins
This week on Biotech Nation, Dr. Neil Kumar, founder and CEO of BridgeBio Pharma. Dr. Kumar emphasizes that genetic diseases, particularly Mendelian diseases caused by single gene mutations, are solvable due to advancements in genetic measurement and understanding. He discusses BridgeBio Pharma's innovative corporate structure, which consists of multiple specialized companies under a centralized infrastructure to efficiently tackle various genetic diseases. This model allows for focused expertise on individual conditions while sharing common resources. Dr. Kumar highlights the company's commitment to using diverse therapeutic modalities, such as small molecules and gene therapies, to develop treatments that address the underlying causes of these diseases.
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Dr. Moira Gunn (00:11):
When I originally spoke with doctor
Neil Kumar, the founder and CEOof Bridge Biopharma, he was very
direct. Genetic diseases aresolvable. Today, we'll hear from
doctor Kumar about what he meansand about the innovative
corporate structure of BridgeBioPharma itself designed for
(00:32):
innovation and success. DoctorKumar, welcome back to the
program.
Dr. Neil Kumar (00:37):
Thank you so much for having me again. I
really appreciate the time.
Dr. Moira Gunn (00:40):
Now you have said to me when we were talking
earlier, and it really hit me, Ihave to say, genetic diseases
are solvable. What do you meanby genetic diseases, and why do
you say they're solvable?
Dr. Neil Kumar (00:52):
Yeah. So when I talk about genetic disease, what
I'm talking about are mostlyinherited diseases, what we call
Mendelian diseases in ourbusiness. And these are diseases
that you can trace back to thecommon source. So it'd be a
point mutation or a single genethat effectively is driving all
of the pathology that you seefor patients. And the reason
(01:15):
that that's important I mean, ifyou sort of think about it, I'm
a engineer by training, and allof the major advances that have
occurred in any engineeringdiscipline come when you can
measure things.
When you can you know, chemicalengineering, for instance, it's
like we used to put stuff in areactor and then try to get
plastic out of it. And then westarted to be able to measure
temperature and pressure and allsorts of things. And then
(01:36):
reliably, we could understandwhat the system was doing and
therefore solve problems. Forthese types of diseases, we can
measure everything that goes onfrom the beginning, the insult,
which is the mutation, to what'shappening inside of a cell, and
you're made up of trillions ofcells, to then what the cells
are doing at a tissue level,because you've got all sorts of
tissues, could be the heart,could be the kidney, etcetera,
(01:57):
to then ultimately what'shappening for the patient. And
because we can describe thecondition or the disease with
that level of clarity, that isprimarily what makes it
solvable.
So we know what's driving and weknow how we might be able to,
what we call it, bridge bio,target the disease at its
source. So effectively take thecausal driver and reverse it if
(02:18):
it got too much of it or, youknow, obviously to turn it up if
you got too little of it. So thethe the the the simplicity with
which we can describe theseconditions is effectively
showing you that they aresolvable, unlike a whole variety
of other conditions where theymay be some genetics, some
environment, some okay. I youknow, there was some acute
(02:39):
injury, you know, physicalinjury of some sorts. These are
much simpler diseases.
Dr. Moira Gunn (02:44):
So this is the area in which Bridge Biopharma
is focusing, and I shouldn'thave said that just coming off
of much simpler diseases becausethere are no simple diseases.
And, looks like a typicalbiotech in the sense that
you've, got 2 drugs alreadydeveloped and approved. You've
got 20 more drug candidates inthe pipeline, but that's sort of
(03:07):
where typical biotech companystops for me. In fact, BridgeBio
is a number of companies.
Dr. Neil Kumar (03:15):
That's right. And, you know, what we were
trying to do like any biotech orstartup, we were trying to solve
a problem that was immediatelyin front of us that we couldn't
solve any other normal way, Isuppose. So, think about when we
started about 8 and a half yearsago, many of us were in a
venture capital firm. We wereworking in the same area of
(03:36):
genetic disease. And every timewe had an idea, we would start 1
company at a time, and that is avery long process.
You go to the venturecapitalists. You get approval.
You build the company. You findspace. You hire in chemist,
etcetera, etcetera.
And so that's a couple years,and then you have another idea,
and you take another coupleyears to do it. And another
idea, you take another coupleyears to do it. And each idea
(03:57):
needs to be big enough that itcan kinda stand on its own and
potentially go public or getbought by pharma, etcetera.
Whereas, when we were looking atthe playing field at that time
and when I say playing field, Imean all of the wonderful work
that was being done in academiathat provided the substrate for
new novel drug discovery andcreation, we said, man, we we
(04:17):
can't wait to just start eachcompany every time. It's gonna
take us decades to do this.
So can we start 1 company thatgoes after all of this
opportunity at the same time?And our our thought at the time,
and I think we were we've beenwrong on a lot of stuff, but we
were right on this, was thatever cheaper genome and exome
sequencing coupled with all ofthese amazing databases like the
UK Biobank and Finjan and whatthe US is doing in terms of
(04:41):
sequencing all these genomes andputting them together with
hospital systems. All of thatinformation was gonna create
even more opportunity for us andthat we needed to create 1 thing
that we could push it allforward. Okay. So now how do you
do that?
You have to do a couple ofthings. 1st is you have to have
some centralized infrastructure,so you've got all these
different ideas that you'repushing forward at the same
time. But the second thing youneed to do is you need to
(05:03):
preserve focus at the level ofeach biology because biotech
wins in my mind because you havesuper specialists that just
wanna solve this condition. So Ican be working on ATTR
cardiomyopathy. I'm an expertthere.
I could be working onpantothenic kinase deficiency. A
separate set of people areexpert there and on and on and
on down the line for the diseasewe work on. So the way we solved
(05:24):
focus at the level of eachbiology was we housed each idea
in a separate company oraffiliate. And then the way we
solved for diversification orbeing able to take on all of
these ideas at the same time wasthat we provided a centralized
infrastructure that took care ofthe things that were common
across all of the ideas. Couldbe manufacturing, could be
(05:46):
finance, could be etcetera,etcetera.
So that's kinda how we set itup, and that that's really what
gave rise to the funky to thefunky corporate structure.
Dr. Moira Gunn (05:54):
I don't know if it's funky.
Dr. Neil Kumar (05:56):
I don't know
Dr. Moira Gunn (05:56):
if it's but but if anybody's worked in a large
organization, you see that theorganization thinks it owns all
the resources. Where the theresources are interchangeable
and and supportive. Great. Thoseare those you're working at the
BridgeBioPharma level. But thenin the various companies, you
got a hard time saying, hey.
(06:17):
You gotta give me your guy. It'slike, no. I don't. I got my old
company.
Dr. Neil Kumar (06:21):
Yeah.
Dr. Moira Gunn (06:21):
I think we're really speaking to something
that breaks through what hasbeen the traditional idea of a
corporate structure.
Dr. Neil Kumar (06:28):
Well, I mean, I think it's important that you
say that there's a a wonderfulbook, that was written by,
Jeffrey West. He's the presidentof the Santa Fe Institute called
Scale. And he goes through andhe just he he tries to analyze
every single thing on earth,basically, and understand why it
(06:49):
tops out at a certain size.Right? So certain things scale,
like, you know, x to the 3rd,but, you know, you can you can
only transport over, you know,let's say, x.
And so, like, there there'll belimits to the size of a human,
for instance, or the size of acity. And what he finds is if
for corporations, what happensis as you get larger, you try to
centralize as much as possiblebecause you're going for
(07:10):
economies of scale. But thatcentralization in and of itself
is what prevents new innovation,which tends to flourish in
decentralized models. Anddecentralized models have a
different property, noteconomies of scale, but returns
to scale. They actually getbigger the larger they get.
And and most companies areeconomies of scale centralized,
and ultimately, most companiesaren't along around for a long
(07:33):
time. Right? The biggestcompanies today are not gonna be
around 30, 40 years from now.But if you can keep them
decentralized, you keep thatinnovation engine going. And
then the challenge that we haveright now is how do you marry
that with something likecommercial, which benefits much
more from centralization.
And we're gonna have to solvethat, on a go forward basis, but
it'll be in, you know, sort ofan interesting corporate
(07:53):
experiment.
Dr. Moira Gunn (07:54):
So at any rate, you've got this broad portfolio
of disease areas. And so let'slet's go across those diseases
because it's 1 thing to say,well, all the genetics and all
the problem. But you recognize alot of of diseases going across
the disease area.
Dr. Neil Kumar (08:12):
Yeah. Exactly. So, I mean, I just give you some
examples of our later stageprograms, but 1 of the earliest
forays, we made was into thearea of precision cardiology.
And, cardiology is almost wheretoday cancer might have been 20
years ago in the sense thatthese broad diseases like heart
failure or heart failure willpreserve ejection fraction.
(08:34):
We're now realizing ourdifferent genetic
subpopulations.
And I had done some work onthat, as a venture capitalist
before, and so 1 of the areasthat we wanted to get involved
with at the start was an ATTRcardiomyopathy. So here's a
really good example of what I'mtalking about with well
described condition. You have inall situations, a destabilizing
(08:55):
mutation in a tetramer in yourblood. And every single time a
patient has that destabilizingmutation, they get this disease.
Right?
And all we're doing is we'rerestabilizing the destabilized
tetramer. So that is geneticstelling you what's causative and
ultimately the ability for asmall molecule therapy in this
case to reverse the causaldriver of the condition. You
(09:18):
know, analogously, inachondroplasia, which is another
condition that is the mostcommon form of dwarfism, you
have a gain of function mutationin a receptor and there we're
just inhibiting that gained offunction with a small molecule
inhibitor. So again, a very verystraightforward therapeutic
hypothesis. It almost tells youhow robustly we understand the
(09:40):
disease.
So it's like every time you havethe disease, in the case of ATTR
cardiomyopathy or the conditionin the case of achondroplasia,
you know that it's being drivenby this thing, and we're just
basically trying to take thatthing that's driving it and and
reverse its effects.
Dr. Moira Gunn (09:55):
Now you said small molecule. It means you're
going after pills. Just simplepills that people can take. Is
that part of the plan? Try toget it into a small molecule?
Dr. Neil Kumar (10:05):
Yeah. It's a it's that's a great question.
So, like, we we we say, a bridgethat we're a modality agnostic,
meaning we'll use a smallmolecule. We'll use an antibody.
We'll use a gene therapy.
We'll use that on an enzymereplacement therapy, but we'll
use anything that allows us toget most quickly to the
marketplace and serve patientsmost productively. So in some
(10:25):
cases, that is a small molecule.In many cases, it's a small
molecule because bridge kind ofgoes after the things that are
overlooked by everyone else.That's what we pride ourselves.
We're like, you know, theunderdog people.
So, you know, small moleculesare not sexy anymore. Gene
editing is sexy right now. Andso if you're gene editing, you
probably can find funds to pushit into the clinic. But if
(10:45):
you've got a small molecule thatcan really reliably serve
patients, chances are not a lotof VCs are super excited about
that. That's where we come in.
So we have probably have 80% ofour portfolio small molecule,
but we do a good deal of genetherapy as well. And, really, it
comes down effectively toworking from the marketplace
backwards and saying, what isultimately the right way to
(11:08):
solve this condition? In thecase of TTR, we believe it's a
small molecule because it canaddress the destabilization of a
tetramer, but it keeps thetetramer around, which is an
important thing. In the case ofcongenital adrenal hyperplasia,
which is disease we work on,which many of your listeners may
not have heard of, but is a verycommon inherited disease, gene
(11:28):
therapy is the only way we canthink of going after because
you're missing something insidethe cell. And it's really hard
with a small molecule to pick upsomething that's missing.
With a gene therapy, we canprovide that inside of the cell.
So it really comes down to thebiology and then what we could
do for patients that's that'sdifferentiated. And and, yeah,
that's how we that's how wechoose the the mode.
Dr. Moira Gunn (11:50):
I love how sometimes you're like, oh, yeah.
I'm I'm a venture capitalist,and I do, you know, and I do
this. And sometimes you're like,they, those venture capitalists
over there. How is being who youare as both, how has that
evolved with your experiencehere with Bridge Biopharma?
Dr. Neil Kumar (12:07):
Well, I was very lucky to to, sort of join the
industry and, to join within thecontext of a firm. It's called
Third Rock Ventures that I thinkwas really doing wonderful
things for innovation andpatience. But in all cases, I I
would say that when you'reworking inside of some system,
in this case, venture capital,you see both the benefits and
(12:29):
the limitations. And thelimitation as compared to a
company construct like we are isfirst and foremost that a
venture capitalist needs to takesomething on and then sell it at
some point to the public marketsor to pharma. And hedge funds
need to obviously avail of somecatalyst or some uptick in
valuation that occurs on, let'ssay, a yearly basis or a
(12:51):
biyearly basis.
But what can a company do? Acompany can step back and say,
I'm on a 14 year journey here,right, from start idea all the
way to marketed product. And howdo I assess that 14 year
journey? I do it through theveracity of the sciences, the
high probability technicalsuccess high enough. And I do it
through trying to understandwhat the overall value of the
(13:12):
program is.
And I think that venturecapitalists get caught up in
small bunches of value, whichtherefore drives them to
inefficiencies that if they werehanging on to the program for
all 14 years, they wouldn'tnecessarily do. So let me be
specific about that. It's like,you know, when you're out here
next, you could drive down thefreeway. We call it the 101 out
here between the the burbs andand downtown San Francisco, and
(13:35):
you see all these big buildings.Right?
Big signs. And many of thosecompanies are not that large,
but they are spending inordinateamount of money on, like, a
really nice facility.
Dr. Moira Gunn (13:46):
Yeah. The size.
Dr. Neil Kumar (13:47):
The size, the facility, all the and why are
they doing that? It's not sillybecause everyone's doing it, so
there must be a reason. Thereason they're doing it is
that's kind of a biomarker ofsuccess. It's like, oh, wow. We
can't we are a big company.
We can go public. It looks greatfor investors, and therefore,
investors are able to make moneyon that, and they're able to do
good science too. But if youreally just cared about the NPV,
(14:08):
the net present value, how do Imost efficiently move the drug
from a to b, b being themarketplace? You wouldn't sign
up all those big buildings. Youtake a low slung lab like we
have somewhere near Palo Alto,and you try to get the minimum
number of people that just workon it.
And if it didn't work, you'dkill it and move on to the next
project. But in the case of asingle asset company or a
(14:29):
company that only has a coupleideas, they never really wanna
kill that idea. So you have alot of inefficiencies that
derive from that system thatotherwise is a really positive
system. But that that that's whyI say sometimes us, sometimes I
say them, because I sort ofstraddle those those 2 worlds.
Dr. Moira Gunn (14:47):
Well, you're either gonna be embraced by both
or rejected by both. So goodluck to you, Neil, on that. But
anyway, the, now you saidsomething earlier about, you
know, out there getting thedata, data out there, putting it
together. You know, There's awhole lot of data going on at
Bridge BioPharma, and sometimesthat data, a lot of people can
(15:10):
use or multiple people can use.Other times, no, it's very
specific to what you're workingon.
Let's talk about that. How do weget the data we need to solve
these genetic diseases?
Dr. Neil Kumar (15:23):
It's a great question. Actually, it begins
with not us. It begins with thewonderful work that's occurring,
that the NIH has funded, thatMHRA and others have funded,
outside of the US and in placeslike the UK and elsewhere, and
the wonderful work that's beingdone in academia. So the data
that's occurring there iseffectively the genetic data, so
(15:47):
what is it that is drivingdisease and these big databases
that I alluded to earlier. Andit's also the elucidation of a
mechanism.
So a great academic will belooking at a disease, and
they'll spend 10 years trying tofigure out precisely what are
these mutations doing. And it'sreally at that moment where they
understand what the mutationsare doing and they understand
(16:10):
how important the geneticsignature is for this disease
that we become involved. Sothat's the first batch of data.
We don't we don't create it. Allwe do is we look at it through
subscriptions to databases,through 22 university
partnerships, and a lot of myjob and everyone else's job at
this company is to just go outand visit academics and talk to
(16:31):
them about what their idea is tosolve condition x or y, which
makes the job just absolutelywonderful.
It's a like, that's that's agreat that's a great job. Then
the data that we generate has todo with how do we manipulate the
system to make it better. Sothat person, the academic, let's
say, he or she has defined theplaying field. And now we're
(16:52):
coming in and saying, well, howdo we change the playing field
so we can better the patient?That starts with data that's
preclinical in and aroundcellular biology, mechanism goes
all the way to animal models.
And then, obviously, the secondbig piece of data generation is
clinical data generation, thatthat we that we take forward.
And that kind of nicely tiesback to the genetics because
(17:13):
we're sequencing all of ourpatients, trying to understand
whether our understanding of thegenetics that we started the
program with continues to holdup in the context of therapeutic
intervention. So that's that'sthe cool part is is really a lot
of the data that we're thatwe're working with is data
that's coming from, you know,the geniuses of of whose
shoulders we stand on.
Dr. Moira Gunn (17:33):
Now you did say to me earlier, though, that
while we all think that thesescientific researchers at
universities, in in academia arereally doing the the drug
discovery. That's not reallytrue.
Dr. Neil Kumar (17:47):
Yeah. Well, you know, drug discovery and
development is, like, thebiggest team sport I think I've
ever seen. We talk about thisconcept of a swarm in, at
BridgeBio. It's it's kind oflike, it's it's it's, you know,
it's it's sort of like there'sno 1 individual who can really
understand everything that'sgoing on all the way from, you
(18:09):
know, sort of basic preclinicalbiology all the way through,
getting a drug approved. So whatI mean what I meant by that is
academics do a very good jobtypically of understanding the
disease condition.
What they are not trained indoing is actually creating the
chemical molecule, the smallmolecule or the gene therapy,
that ultimately is theintervention that's gonna get
(18:30):
into the clinic. Now, you know,so so the majority vast majority
of drugs, those are coming fromcompanies that have those skill
sets. Right? Medicinal chemistsand and others and expertise in
dealing with the regulators,etcetera. But what that doesn't
mean is that the core idea,let's say someone elucidated
this mechanism or this pathwaydidn't come from academia.
(18:52):
All I'm saying is it's a teamsport. I think without academia,
BridgeBio would be nothing, And,hopefully, the academics we
partner with would agree thatwithout BridgeBio, the ultimate
manifestation of their dreams,which is a drug that's helping
patients wouldn't havenecessarily been as easy as
well. So it all works as as weall come together.
Dr. Moira Gunn (19:10):
So in a sense, yes, all of those scientists are
out there figuring out thescience. What's wrong? How does
it work? And then you go, well,thanks. I think we can we might
be able to build a drug forthat.
Now you've gotta do more scienceto make that work, but it's like
it's 2 different things. It's 2different things in a sense, but
together. Yeah.
Dr. Neil Kumar (19:31):
There's actually 2 interesting, things to mention
here. 1 is that universitiesover the course of the last
maybe 15 years started torealize that they too could
productively be involved withthe early stages of drug
discovery. So you've seen someabsolutely wonderful institutes
arise like, Dana Farber has 1,MD Anderson has 1 that we
(19:53):
partner with where they actuallytake ideas from some of the
academics and actually do someof the early chemistry
themselves. And then they'lllicense it out later to, to a
pharma company. So that's that's1 trend that I think is worth
paying attention to.
The other trend that's worthpaying attention to is the fact
that with newer modalities likegene therapy, academics are
actually able to take it furtherinside their own labs. So for
(20:15):
instance, when we partner with,a luminary like at a University,
Massachusetts Amherst. He'salready advanced to gene therapy
a year away from the clinic,whereas if I took on a small
molecule, it may still be 3, 4years, away from the clinic. So
there's some really, really neat
Dr. Moira Gunn (20:33):
And when we say away from the clinic, we mean
first in humans. We're actuallygonna try it in humans.
Dr. Neil Kumar (20:38):
1st in human, which is another 5, 6 years from
the marketplace. So, I mean, thetimelines you're talking about
here, that's a good it's a goodreminder. You know, an academic
could work on a disease for 20years and really crack it, and
then we come in and we'll workon a drug for 10 years. And
together, that process allowsfor a marketed product maybe
some 30 years later. But but,you know, that cycle time is
(21:01):
accelerating the more and morewe have all of this information
that describes what's happeningin a molecular level.
So that that's the excitingthing about today.
Dr. Moira Gunn (21:10):
Well, I have 1 question, and that is it sounds
funny, but because we know thatBridge Biopharma is publicly
traded. If I buy a share ofBridge Biopharma, am I, are I
getting parts of those othercompanies? How does that work?
What does that mean?
Dr. Neil Kumar (21:30):
It's a great question. Yeah. So we
effectively wholly own thesecompanies now. So, yeah, it's
it's it's almost like having adrug portfolio. It's just that
we continue to use the companystructure so that we can provide
incentives at the level of eachprogram.
And what that means is havingfor reasons that we don't have
(21:51):
to get into, but for for legalstructural reasons, it allows me
to say for my employees that areworking on, say, pantothenic
kinase deficiency, they'll onlygonna get rewarded if that drug
advances, but not necessarily ifmy TTR drug advances. And the
reason that that's important isthat that they really focus on
what they're doing. It's focusedat the level of their biology,
(22:13):
and it takes away from this sortof, I would say, confusion that
you get in large pharma where,yeah, I'm working on this
project, but it doesn't reallyaffect my, you know, my my
overall compensation, in a in ameaningful way. This this this
aligns all incentives very well.
Dr. Moira Gunn (22:30):
Well, doctor Kumar, this has been terrific.
You know you're always welcomeon TechNation. I hope you, come
back and see us again.
Dr. Neil Kumar (22:36):
Thanks so much for having me. I really
appreciate it.
Dr. Moira Gunn (22:39):
Doctor Neil Kumar is the founder and CEO of
Bridge BioPharma. Moreinformation is available on the
web@bridgebio.com.
When I originally spoke with doctor
Neil Kumar, the founder and CEOof Bridge Biopharma, he was very
direct. Genetic diseases aresolvable. Today, we'll hear from
doctor Kumar about what he meansand about the innovative
corporate structure of BridgeBioPharma itself designed for
(00:32):
innovation and success. DoctorKumar, welcome back to the
program.
Dr. Neil Kumar (00:37):
Thank you so much for having me again. I
really appreciate the time.
Dr. Moira Gunn (00:40):
Now you have said to me when we were talking
earlier, and it really hit me, Ihave to say, genetic diseases
are solvable. What do you meanby genetic diseases, and why do
you say they're solvable?
Dr. Neil Kumar (00:52):
Yeah. So when I talk about genetic disease, what
I'm talking about are mostlyinherited diseases, what we call
Mendelian diseases in ourbusiness. And these are diseases
that you can trace back to thecommon source. So it'd be a
point mutation or a single genethat effectively is driving all
of the pathology that you seefor patients. And the reason
(01:15):
that that's important I mean, ifyou sort of think about it, I'm
a engineer by training, and allof the major advances that have
occurred in any engineeringdiscipline come when you can
measure things.
When you can you know, chemicalengineering, for instance, it's
like we used to put stuff in areactor and then try to get
plastic out of it. And then westarted to be able to measure
temperature and pressure and allsorts of things. And then
(01:36):
reliably, we could understandwhat the system was doing and
therefore solve problems. Forthese types of diseases, we can
measure everything that goes onfrom the beginning, the insult,
which is the mutation, to what'shappening inside of a cell, and
you're made up of trillions ofcells, to then what the cells
are doing at a tissue level,because you've got all sorts of
tissues, could be the heart,could be the kidney, etcetera,
(01:57):
to then ultimately what'shappening for the patient. And
because we can describe thecondition or the disease with
that level of clarity, that isprimarily what makes it
solvable.
So we know what's driving and weknow how we might be able to,
what we call it, bridge bio,target the disease at its
source. So effectively take thecausal driver and reverse it if
(02:18):
it got too much of it or, youknow, obviously to turn it up if
you got too little of it. So thethe the the the simplicity with
which we can describe theseconditions is effectively
showing you that they aresolvable, unlike a whole variety
of other conditions where theymay be some genetics, some
environment, some okay. I youknow, there was some acute
(02:39):
injury, you know, physicalinjury of some sorts. These are
much simpler diseases.
Dr. Moira Gunn (02:44):
So this is the area in which Bridge Biopharma
is focusing, and I shouldn'thave said that just coming off
of much simpler diseases becausethere are no simple diseases.
And, looks like a typicalbiotech in the sense that
you've, got 2 drugs alreadydeveloped and approved. You've
got 20 more drug candidates inthe pipeline, but that's sort of
(03:07):
where typical biotech companystops for me. In fact, BridgeBio
is a number of companies.
Dr. Neil Kumar (03:15):
That's right. And, you know, what we were
trying to do like any biotech orstartup, we were trying to solve
a problem that was immediatelyin front of us that we couldn't
solve any other normal way, Isuppose. So, think about when we
started about 8 and a half yearsago, many of us were in a
venture capital firm. We wereworking in the same area of
(03:36):
genetic disease. And every timewe had an idea, we would start 1
company at a time, and that is avery long process.
You go to the venturecapitalists. You get approval.
You build the company. You findspace. You hire in chemist,
etcetera, etcetera.
And so that's a couple years,and then you have another idea,
and you take another coupleyears to do it. And another
idea, you take another coupleyears to do it. And each idea
(03:57):
needs to be big enough that itcan kinda stand on its own and
potentially go public or getbought by pharma, etcetera.
Whereas, when we were looking atthe playing field at that time
and when I say playing field, Imean all of the wonderful work
that was being done in academiathat provided the substrate for
new novel drug discovery andcreation, we said, man, we we
(04:17):
can't wait to just start eachcompany every time. It's gonna
take us decades to do this.
So can we start 1 company thatgoes after all of this
opportunity at the same time?And our our thought at the time,
and I think we were we've beenwrong on a lot of stuff, but we
were right on this, was thatever cheaper genome and exome
sequencing coupled with all ofthese amazing databases like the
UK Biobank and Finjan and whatthe US is doing in terms of
(04:41):
sequencing all these genomes andputting them together with
hospital systems. All of thatinformation was gonna create
even more opportunity for us andthat we needed to create 1 thing
that we could push it allforward. Okay. So now how do you
do that?
You have to do a couple ofthings. 1st is you have to have
some centralized infrastructure,so you've got all these
different ideas that you'repushing forward at the same
time. But the second thing youneed to do is you need to
(05:03):
preserve focus at the level ofeach biology because biotech
wins in my mind because you havesuper specialists that just
wanna solve this condition. So Ican be working on ATTR
cardiomyopathy. I'm an expertthere.
I could be working onpantothenic kinase deficiency. A
separate set of people areexpert there and on and on and
on down the line for the diseasewe work on. So the way we solved
(05:24):
focus at the level of eachbiology was we housed each idea
in a separate company oraffiliate. And then the way we
solved for diversification orbeing able to take on all of
these ideas at the same time wasthat we provided a centralized
infrastructure that took care ofthe things that were common
across all of the ideas. Couldbe manufacturing, could be
(05:46):
finance, could be etcetera,etcetera.
So that's kinda how we set itup, and that that's really what
gave rise to the funky to thefunky corporate structure.
Dr. Moira Gunn (05:54):
I don't know if it's funky.
Dr. Neil Kumar (05:56):
I don't know
Dr. Moira Gunn (05:56):
if it's but but if anybody's worked in a large
organization, you see that theorganization thinks it owns all
the resources. Where the theresources are interchangeable
and and supportive. Great. Thoseare those you're working at the
BridgeBioPharma level. But thenin the various companies, you
got a hard time saying, hey.
(06:17):
You gotta give me your guy. It'slike, no. I don't. I got my old
company.
Dr. Neil Kumar (06:21):
Yeah.
Dr. Moira Gunn (06:21):
I think we're really speaking to something
that breaks through what hasbeen the traditional idea of a
corporate structure.
Dr. Neil Kumar (06:28):
Well, I mean, I think it's important that you
say that there's a a wonderfulbook, that was written by,
Jeffrey West. He's the presidentof the Santa Fe Institute called
Scale. And he goes through andhe just he he tries to analyze
every single thing on earth,basically, and understand why it
(06:49):
tops out at a certain size.Right? So certain things scale,
like, you know, x to the 3rd,but, you know, you can you can
only transport over, you know,let's say, x.
And so, like, there there'll belimits to the size of a human,
for instance, or the size of acity. And what he finds is if
for corporations, what happensis as you get larger, you try to
centralize as much as possiblebecause you're going for
(07:10):
economies of scale. But thatcentralization in and of itself
is what prevents new innovation,which tends to flourish in
decentralized models. Anddecentralized models have a
different property, noteconomies of scale, but returns
to scale. They actually getbigger the larger they get.
And and most companies areeconomies of scale centralized,
and ultimately, most companiesaren't along around for a long
(07:33):
time. Right? The biggestcompanies today are not gonna be
around 30, 40 years from now.But if you can keep them
decentralized, you keep thatinnovation engine going. And
then the challenge that we haveright now is how do you marry
that with something likecommercial, which benefits much
more from centralization.
And we're gonna have to solvethat, on a go forward basis, but
it'll be in, you know, sort ofan interesting corporate
(07:53):
experiment.
Dr. Moira Gunn (07:54):
So at any rate, you've got this broad portfolio
of disease areas. And so let'slet's go across those diseases
because it's 1 thing to say,well, all the genetics and all
the problem. But you recognize alot of of diseases going across
the disease area.
Dr. Neil Kumar (08:12):
Yeah. Exactly. So, I mean, I just give you some
examples of our later stageprograms, but 1 of the earliest
forays, we made was into thearea of precision cardiology.
And, cardiology is almost wheretoday cancer might have been 20
years ago in the sense thatthese broad diseases like heart
failure or heart failure willpreserve ejection fraction.
(08:34):
We're now realizing ourdifferent genetic
subpopulations.
And I had done some work onthat, as a venture capitalist
before, and so 1 of the areasthat we wanted to get involved
with at the start was an ATTRcardiomyopathy. So here's a
really good example of what I'mtalking about with well
described condition. You have inall situations, a destabilizing
(08:55):
mutation in a tetramer in yourblood. And every single time a
patient has that destabilizingmutation, they get this disease.
Right?
And all we're doing is we'rerestabilizing the destabilized
tetramer. So that is geneticstelling you what's causative and
ultimately the ability for asmall molecule therapy in this
case to reverse the causaldriver of the condition. You
(09:18):
know, analogously, inachondroplasia, which is another
condition that is the mostcommon form of dwarfism, you
have a gain of function mutationin a receptor and there we're
just inhibiting that gained offunction with a small molecule
inhibitor. So again, a very verystraightforward therapeutic
hypothesis. It almost tells youhow robustly we understand the
(09:40):
disease.
So it's like every time you havethe disease, in the case of ATTR
cardiomyopathy or the conditionin the case of achondroplasia,
you know that it's being drivenby this thing, and we're just
basically trying to take thatthing that's driving it and and
reverse its effects.
Dr. Moira Gunn (09:55):
Now you said small molecule. It means you're
going after pills. Just simplepills that people can take. Is
that part of the plan? Try toget it into a small molecule?
Dr. Neil Kumar (10:05):
Yeah. It's a it's that's a great question.
So, like, we we we say, a bridgethat we're a modality agnostic,
meaning we'll use a smallmolecule. We'll use an antibody.
We'll use a gene therapy.
We'll use that on an enzymereplacement therapy, but we'll
use anything that allows us toget most quickly to the
marketplace and serve patientsmost productively. So in some
(10:25):
cases, that is a small molecule.In many cases, it's a small
molecule because bridge kind ofgoes after the things that are
overlooked by everyone else.That's what we pride ourselves.
We're like, you know, theunderdog people.
So, you know, small moleculesare not sexy anymore. Gene
editing is sexy right now. Andso if you're gene editing, you
probably can find funds to pushit into the clinic. But if
(10:45):
you've got a small molecule thatcan really reliably serve
patients, chances are not a lotof VCs are super excited about
that. That's where we come in.
So we have probably have 80% ofour portfolio small molecule,
but we do a good deal of genetherapy as well. And, really, it
comes down effectively toworking from the marketplace
backwards and saying, what isultimately the right way to
(11:08):
solve this condition? In thecase of TTR, we believe it's a
small molecule because it canaddress the destabilization of a
tetramer, but it keeps thetetramer around, which is an
important thing. In the case ofcongenital adrenal hyperplasia,
which is disease we work on,which many of your listeners may
not have heard of, but is a verycommon inherited disease, gene
(11:28):
therapy is the only way we canthink of going after because
you're missing something insidethe cell. And it's really hard
with a small molecule to pick upsomething that's missing.
With a gene therapy, we canprovide that inside of the cell.
So it really comes down to thebiology and then what we could
do for patients that's that'sdifferentiated. And and, yeah,
that's how we that's how wechoose the the mode.
Dr. Moira Gunn (11:50):
I love how sometimes you're like, oh, yeah.
I'm I'm a venture capitalist,and I do, you know, and I do
this. And sometimes you're like,they, those venture capitalists
over there. How is being who youare as both, how has that
evolved with your experiencehere with Bridge Biopharma?
Dr. Neil Kumar (12:07):
Well, I was very lucky to to, sort of join the
industry and, to join within thecontext of a firm. It's called
Third Rock Ventures that I thinkwas really doing wonderful
things for innovation andpatience. But in all cases, I I
would say that when you'reworking inside of some system,
in this case, venture capital,you see both the benefits and
(12:29):
the limitations. And thelimitation as compared to a
company construct like we are isfirst and foremost that a
venture capitalist needs to takesomething on and then sell it at
some point to the public marketsor to pharma. And hedge funds
need to obviously avail of somecatalyst or some uptick in
valuation that occurs on, let'ssay, a yearly basis or a
(12:51):
biyearly basis.
But what can a company do? Acompany can step back and say,
I'm on a 14 year journey here,right, from start idea all the
way to marketed product. And howdo I assess that 14 year
journey? I do it through theveracity of the sciences, the
high probability technicalsuccess high enough. And I do it
through trying to understandwhat the overall value of the
(13:12):
program is.
And I think that venturecapitalists get caught up in
small bunches of value, whichtherefore drives them to
inefficiencies that if they werehanging on to the program for
all 14 years, they wouldn'tnecessarily do. So let me be
specific about that. It's like,you know, when you're out here
next, you could drive down thefreeway. We call it the 101 out
here between the the burbs andand downtown San Francisco, and
(13:35):
you see all these big buildings.Right?
Big signs. And many of thosecompanies are not that large,
but they are spending inordinateamount of money on, like, a
really nice facility.
Dr. Moira Gunn (13:46):
Yeah. The size.
Dr. Neil Kumar (13:47):
The size, the facility, all the and why are
they doing that? It's not sillybecause everyone's doing it, so
there must be a reason. Thereason they're doing it is
that's kind of a biomarker ofsuccess. It's like, oh, wow. We
can't we are a big company.
We can go public. It looks greatfor investors, and therefore,
investors are able to make moneyon that, and they're able to do
good science too. But if youreally just cared about the NPV,
(14:08):
the net present value, how do Imost efficiently move the drug
from a to b, b being themarketplace? You wouldn't sign
up all those big buildings. Youtake a low slung lab like we
have somewhere near Palo Alto,and you try to get the minimum
number of people that just workon it.
And if it didn't work, you'dkill it and move on to the next
project. But in the case of asingle asset company or a
(14:29):
company that only has a coupleideas, they never really wanna
kill that idea. So you have alot of inefficiencies that
derive from that system thatotherwise is a really positive
system. But that that that's whyI say sometimes us, sometimes I
say them, because I sort ofstraddle those those 2 worlds.
Dr. Moira Gunn (14:47):
Well, you're either gonna be embraced by both
or rejected by both. So goodluck to you, Neil, on that. But
anyway, the, now you saidsomething earlier about, you
know, out there getting thedata, data out there, putting it
together. You know, There's awhole lot of data going on at
Bridge BioPharma, and sometimesthat data, a lot of people can
(15:10):
use or multiple people can use.Other times, no, it's very
specific to what you're workingon.
Let's talk about that. How do weget the data we need to solve
these genetic diseases?
Dr. Neil Kumar (15:23):
It's a great question. Actually, it begins
with not us. It begins with thewonderful work that's occurring,
that the NIH has funded, thatMHRA and others have funded,
outside of the US and in placeslike the UK and elsewhere, and
the wonderful work that's beingdone in academia. So the data
that's occurring there iseffectively the genetic data, so
(15:47):
what is it that is drivingdisease and these big databases
that I alluded to earlier. Andit's also the elucidation of a
mechanism.
So a great academic will belooking at a disease, and
they'll spend 10 years trying tofigure out precisely what are
these mutations doing. And it'sreally at that moment where they
understand what the mutationsare doing and they understand
(16:10):
how important the geneticsignature is for this disease
that we become involved. Sothat's the first batch of data.
We don't we don't create it. Allwe do is we look at it through
subscriptions to databases,through 22 university
partnerships, and a lot of myjob and everyone else's job at
this company is to just go outand visit academics and talk to
(16:31):
them about what their idea is tosolve condition x or y, which
makes the job just absolutelywonderful.
It's a like, that's that's agreat that's a great job. Then
the data that we generate has todo with how do we manipulate the
system to make it better. Sothat person, the academic, let's
say, he or she has defined theplaying field. And now we're
(16:52):
coming in and saying, well, howdo we change the playing field
so we can better the patient?That starts with data that's
preclinical in and aroundcellular biology, mechanism goes
all the way to animal models.
And then, obviously, the secondbig piece of data generation is
clinical data generation, thatthat we that we take forward.
And that kind of nicely tiesback to the genetics because
(17:13):
we're sequencing all of ourpatients, trying to understand
whether our understanding of thegenetics that we started the
program with continues to holdup in the context of therapeutic
intervention. So that's that'sthe cool part is is really a lot
of the data that we're thatwe're working with is data
that's coming from, you know,the geniuses of of whose
shoulders we stand on.
Dr. Moira Gunn (17:33):
Now you did say to me earlier, though, that
while we all think that thesescientific researchers at
universities, in in academia arereally doing the the drug
discovery. That's not reallytrue.
Dr. Neil Kumar (17:47):
Yeah. Well, you know, drug discovery and
development is, like, thebiggest team sport I think I've
ever seen. We talk about thisconcept of a swarm in, at
BridgeBio. It's it's kind oflike, it's it's it's, you know,
it's it's sort of like there'sno 1 individual who can really
understand everything that'sgoing on all the way from, you
(18:09):
know, sort of basic preclinicalbiology all the way through,
getting a drug approved. So whatI mean what I meant by that is
academics do a very good jobtypically of understanding the
disease condition.
What they are not trained indoing is actually creating the
chemical molecule, the smallmolecule or the gene therapy,
that ultimately is theintervention that's gonna get
(18:30):
into the clinic. Now, you know,so so the majority vast majority
of drugs, those are coming fromcompanies that have those skill
sets. Right? Medicinal chemistsand and others and expertise in
dealing with the regulators,etcetera. But what that doesn't
mean is that the core idea,let's say someone elucidated
this mechanism or this pathwaydidn't come from academia.
(18:52):
All I'm saying is it's a teamsport. I think without academia,
BridgeBio would be nothing, And,hopefully, the academics we
partner with would agree thatwithout BridgeBio, the ultimate
manifestation of their dreams,which is a drug that's helping
patients wouldn't havenecessarily been as easy as
well. So it all works as as weall come together.
Dr. Moira Gunn (19:10):
So in a sense, yes, all of those scientists are
out there figuring out thescience. What's wrong? How does
it work? And then you go, well,thanks. I think we can we might
be able to build a drug forthat.
Now you've gotta do more scienceto make that work, but it's like
it's 2 different things. It's 2different things in a sense, but
together. Yeah.
Dr. Neil Kumar (19:31):
There's actually 2 interesting, things to mention
here. 1 is that universitiesover the course of the last
maybe 15 years started torealize that they too could
productively be involved withthe early stages of drug
discovery. So you've seen someabsolutely wonderful institutes
arise like, Dana Farber has 1,MD Anderson has 1 that we
(19:53):
partner with where they actuallytake ideas from some of the
academics and actually do someof the early chemistry
themselves. And then they'lllicense it out later to, to a
pharma company. So that's that's1 trend that I think is worth
paying attention to.
The other trend that's worthpaying attention to is the fact
that with newer modalities likegene therapy, academics are
actually able to take it furtherinside their own labs. So for
(20:15):
instance, when we partner with,a luminary like at a University,
Massachusetts Amherst. He'salready advanced to gene therapy
a year away from the clinic,whereas if I took on a small
molecule, it may still be 3, 4years, away from the clinic. So
there's some really, really neat
Dr. Moira Gunn (20:33):
And when we say away from the clinic, we mean
first in humans. We're actuallygonna try it in humans.
Dr. Neil Kumar (20:38):
1st in human, which is another 5, 6 years from
the marketplace. So, I mean, thetimelines you're talking about
here, that's a good it's a goodreminder. You know, an academic
could work on a disease for 20years and really crack it, and
then we come in and we'll workon a drug for 10 years. And
together, that process allowsfor a marketed product maybe
some 30 years later. But but,you know, that cycle time is
(21:01):
accelerating the more and morewe have all of this information
that describes what's happeningin a molecular level.
So that that's the excitingthing about today.
Dr. Moira Gunn (21:10):
Well, I have 1 question, and that is it sounds
funny, but because we know thatBridge Biopharma is publicly
traded. If I buy a share ofBridge Biopharma, am I, are I
getting parts of those othercompanies? How does that work?
What does that mean?
Dr. Neil Kumar (21:30):
It's a great question. Yeah. So we
effectively wholly own thesecompanies now. So, yeah, it's
it's it's almost like having adrug portfolio. It's just that
we continue to use the companystructure so that we can provide
incentives at the level of eachprogram.
And what that means is havingfor reasons that we don't have
(21:51):
to get into, but for for legalstructural reasons, it allows me
to say for my employees that areworking on, say, pantothenic
kinase deficiency, they'll onlygonna get rewarded if that drug
advances, but not necessarily ifmy TTR drug advances. And the
reason that that's important isthat that they really focus on
what they're doing. It's focusedat the level of their biology,
(22:13):
and it takes away from this sortof, I would say, confusion that
you get in large pharma where,yeah, I'm working on this
project, but it doesn't reallyaffect my, you know, my my
overall compensation, in a in ameaningful way. This this this
aligns all incentives very well.
Dr. Moira Gunn (22:30):
Well, doctor Kumar, this has been terrific.
You know you're always welcomeon TechNation. I hope you, come
back and see us again.
Dr. Neil Kumar (22:36):
Thanks so much for having me. I really
appreciate it.
Dr. Moira Gunn (22:39):
Doctor Neil Kumar is the founder and CEO of
Bridge BioPharma. Moreinformation is available on the
web@bridgebio.com.
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