March 17, 2025 • 43 mins
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Dr. Kasper Roet's hands-on work at the Dutch Brain Bank informed his leadership at the biotech QurAlis, where three clinical programs targeting specific genetic mechanisms in ALS are now underway. On this episode of the Business of Biotech, Life Science Leader's Ben Comer joins to co-host a conversation with Dr. Roet that goes deep on his company's genetic medicine approach to ALS, and even deeper into his opinions on, and growing influence over, the regulatory environment. Roet says that as the FDA's conservative approach to genetic medicines has pushed clinical trials overseas, he's been inspired to form and lead a consortium of 11-and-growing biotechs seeking regulatory reform through organized meetings and lobbying efforts. Join us for this latest of our BoB@JPM series from San Francisco.
The 2025 BoB@JPM series is supported by Alston & Bird, whose national health care and life sciences practice has more than 100 attorneys actively involved and integrated across the full spectrum of legal disciplines including regulatory, compliance, public policy, transactional, corporate governance, securities, FDA, biotechnology, intellectual property, government investigations, and litigation practice areas. Learn more at www.alston.com.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Ben Comer (00:04):
There's not much metering.
Kasper Roet's confidence in hiscompany's technology can
counter neurological disorderslike ALS.
If his long-standing andhands-on commitment to neuro
research is any indication thatconfidence is well placed.
I'm Ben Comer and I'm MattPillar and this is the Business
of Biotech JPMorgan 2025 edition, and we're here in San
(00:26):
Francisco at the law offices ofAlston & Bird with Dr
Roet, founder and.
Ceo of QurAlis, to explore thewhy behind his optimism.
Dr Roet, thanks for being here.
Matt Pillar (00:38):
My pleasure.
Thanks for inviting me.
Kasper Roet (00:40):
It's our pleasure, dr Root, and I noticed you
rolled the R on the firstpronunciation and then rolled
right back into the straight.
Ben Comer (00:47):
American.
Yeah, you know, I tried it andI thought it sounded a little
funny coming out of my mouth.
I need to practice it some morebefore I pull it back out.
Kasper Roet (00:53):
I give you kudos for even trying.
I appreciate that.
So you've got a very diverseand hands-on background in
pretty much everything thatyou've done hands-on background
in pretty much everything thatyou've done.
And I'm curious about thebeginnings of your career.
Before you got into lifesciences, you started your
career in IT.
Is that correct?
Matt Pillar (01:11):
That is correct.
Kasper Roet (01:13):
So tell us a little bit about that and where, when
and why the pivot from IT intolife sciences occurred.
Matt Pillar (01:23):
My IT life comes from the fact that I have a
passion for computers.
I started that as a very youngchild and when the internet boom
started in the 1990s, I was oneof the few people that knew how
to assemble computers, takethem apart, program them, build
Wi-Fi networks.
And so when I was finishing mybachelor degree at the
(01:47):
University of Amsterdam, me andtwo friends were asked to help
with small companies and studenthouses to set up their IT
infrastructure so that everyonecould get access to the internet
.
So I kind of rolled that into acompany and that became
actually an IT company thatfirst built infrastructure, then
built web applications and thenalso placed IT specialists at
(02:10):
other companies to solve theirproblems.
I had never anticipated beingan entrepreneur before that.
It was kind of a naturalevolution to become an
entrepreneur, and when Irealized how great it was to
actually be able to create yourown visions into reality, I was
caught and I knew I wanted to bean entrepreneur.
Kasper Roet (02:30):
But I also knew.
Matt Pillar (02:31):
I didn't actually want to be an IT entrepreneur
it's my passion.
I've always been on biology andI really wanted to develop
medicine so that we couldactually have a world hopefully
a future world where we don'tsuffer from diseases anymore.
Kasper Roet (02:46):
Yeah Well, let me just say that I think you made
the right choice because yourpersonality lends itself to
medicine.
I covered IT for like 20 yearsand the IT space.
The people that I interviewedin the IT space not nearly as
chill.
As you are right, there'sbigger egos in the IT space than
there are in the life sciences,and so I think you made the
(03:08):
right decision.
Based on what I know about youso far, Good.
Matt Pillar (03:12):
What was your first computer?
My first computer.
You know like I had a Commodore64, but I actually had like a
games computer before that.
I don't think I must haveexplored it with a Comm computer
anymore, but I think that well,I guess I'm an Atari before the
Commodore.
That's like evolved and youtook all this apart.
(03:32):
Yes, I always tried to makethem a little faster and crank
up their memory a little bit soI could play better games.
That was really the bigmotivator, yeah.
Kasper Roet (03:42):
What was your foray when you decided that you
wanted to pursue something inthe life sciences medicine
related?
What was your first foray intothat field?
Matt Pillar (03:53):
My first foray.
You know, I started actuallywith artificial intelligence in
my university track.
But I come from the fields of asmall farm town.
Actually, the first lake thatwas dried out the big lake in
the Netherlands was where I grewup and I had a microscope and I
(04:16):
caught little bugs in the fieldand I was just taking them
apart to see how they work.
And that was really a passionfor me, and not just thinking
the box, but understandingbiology and understanding nature
.
And so I was doing thisartificial intelligence.
But I realized a lot of peopleare probably better at
programming and I realized Ishould just do what I'm really
(04:39):
good at and I decided to studymedical biology again at the
University of Amsterdam and Iloved it the moment I started
that I was just in love with it.
And then after that I enrolledin this IT company.
But I went back and did amaster's in neuroscience and
there I was working in one ofthe former gene therapy labs in
(05:02):
the Netherlands.
The lab of Joost Verhagen wasreally pushing gene therapy
technologies forward.
Because I wanted to translate.
At that moment I already knew Iwanted to make medicine and
gene therapy is actually anultimate medicine and that kind
of got me the exposure in theneuroscience space, because that
(05:24):
is where Yoast was working tomake gene therapies for spinal
cord repair, for paralyzedpeople, and so I did my master's
internship there.
I did a master's internship inUCSD with Mark Trushinsky, a big
gene therapy scientist there,and then I came back to do a PhD
(05:44):
.
But again I wanted to dosomething that was really
translational.
So I started a gene therapy PhDproject which was a
collaboration between theUniversity of Amsterdam, the
Free University, a&t, which wasAmsterdam Molecular Therapeutics
, which later became Unicure,quite a successful gene therapy
company.
(06:04):
At that time they actuallybrought the first gene therapy
into the Western markets forKlaipera, and so I was there at
that time while they were doingthat and I was also
collaborating with Galapagos.
They were part of the project.
Basically it was called theCenter Nolten Project, again to
bring gene therapies to spinalcord repair.
Basically it was called thesensor nolten project, again to
(06:26):
bring gene therapies to spinalcord repair.
And so the institute where Iworked, the nebulous institute
for neuroscience, was actually,um, the.
The director there started thedutch brain bank and the dutch
brain bank is one of I think oneof the best brain banks in the
world, because usually withintwo hours after a donor passes
away, the body is brought to thehospital and we're following an
(06:50):
autopsy protocol to take outbrain and spinal cord and
process that in a certain way,depending on the disease.
And I started to work there andbecame an autopsy coordinator,
which meant that in the middleof the night I would get a phone
call someone has passed away.
Can you please organize theautopsy?
(07:12):
So I would call the families, Iwould call the undertaker, I
would call the neuropathologist,the section assistant, we would
all go to the hospital, wewould receive the body, we would
then look at it and I could seethe impact that all these
neurodegenerative diseases haveon patients talking to their
family, looking at their bodies,looking at their brains,
(07:32):
looking at their spinal cords,taking it apart and sometimes
bringing the tissues back to theinstitute where, sometimes in
the middle of the night,researchers would come to try to
find out things that werehappening in those diseases.
And that really caught me intothe broader neurodegenerative
space.
And so, yeah, that is whatreally started to motivate me,
(07:56):
just the incredible impact thatthose diseases have on those
patients, both on them obviouslythey've passed away at that
point but also on their familiesat that point, but also on
their families and I decided Ido and really specialize in
development of therapies forneurodegenerative diseases.
Ben Comer (08:11):
How did that really hands-on experience at the
Netherlands Brain Bank influenceyour career and where you are
now?
Because that strikes me asunique.
Not everyone in the industryhas that degree of you know
handling a brain that works inneuroscience.
Matt Pillar (08:29):
Yeah, I can tell you it's really helpful right
now because we're working on anautopsy program for our current
trial and I understand how itworks, what it means to have
tissue, how it's processed youknow I'm the CEO, but it's good
to have that type ofunderstanding.
And you know my company is nowcollaborating with the Dutch
(08:51):
Brain Bank.
We just started a program alsofor Fragile X.
We wanted to get tissue fromFragile X patients and the
tissue that we got from thesepatients we've been able to
study and really confirm agenetic target for Fragile X.
I mean that has really helpedme to appreciate the tissue and
really confirm a genetic targetfor Fragile X.
I mean that has really helpedme to appreciate the tissue.
(09:11):
One of the other things that Ireally took away from that is
how often patients aremisdiagnosed, because clinicians
misdiagnose patients based onclinical symptoms.
But once you open up someone'sbody and you look actually on
how the disease looks inside thebody, very often we saw that
the clinical diagnosis was notcorrect.
But a clinical diagnosis oftenstands and so when you get
(09:35):
tissue from a donor, theclinical diagnosis is the
diagnosis.
You have to really read throughthat to see if the pathological
diagnosis is the same, becauseotherwise you're actually
drawing the wrong conclusions onthe materials that you use.
And that's a very practicalpoint where my experience there
has really given me caution oninterpretation of data from
(09:58):
material from donors, and Ithink it's helping us do better
things in Curalis, yeah, and Ithink it's helping us do better
things in Curalis.
Kasper Roet (10:07):
Yeah, so we kind of fast-forwarded to Curalis.
There were a couple of stopsbetween the Dutch Brain Bank and
your founding of Curalis.
Matt Pillar (10:15):
Yeah, again, I knew I wanted to develop medicine
and I realized I know how a lotof companies worked.
I worked as a computerspecialist in a computer company
as a side job.
I was a telephone marketer fora while.
I worked at an investment bank,and so I kind of knew a lot of
(10:38):
different sectors.
Kasper Roet (10:39):
Worked in a bar.
Had no idea how you make atruck.
Matt Pillar (10:42):
And it's like I want to start a company
developing therapeutics, Ireally need to understand how to
make a truck.
And so in the Netherlands oneof the big R&D organizations at
that moment was J&J, who hadtheir Janssen vaccine site there
which was formerly Crucell butwas acquired by J&J just before
(11:04):
that time that I graduated withmy PhD and I applied there and
got a job, first as an assaypotency development team leader
and that kind of progressed intobecoming a technical integrator
and there I learned how you getsomething from research all the
(11:24):
way to the clinic, because Iworked together with Formulation
, phil and ThinHash upstreamprocessing, downstream
processing, clinical assays, qcassays, r&d, cmc, and there, a
couple of years in, I reallyunderstood how you can actually
make a drug and how thepharmaceutical business works
and what type of experts youneed and all of that.
(11:45):
And while I was doing thatC9-472 was discovered big ALS
gene.
My PhD program was spinal cordrepair, gene therapies.
So neuromuscular ALS is aneuromuscular disease and so
it's the same tissues.
But I thought we cannot treatALS because we don't understand
the disease.
Kasper Roet (12:05):
But while I was at JMJ, a big ALS gene was
discovered and then rapidly, 300ALS genes were discovered.
Matt Pillar (12:13):
And I'm a big data person, probably because of my
passion for computers, and so Istarted looking at that and I
thought this is incredible.
We have the genetics of thedisease.
I could see pathways emerge.
I could see this is incredible.
We have the genetics of thedisease, I could see pathways
emerge.
I could see disease mechanismsemerge.
And so in my hobby time I tookpublished data sets from
post-mortem tissues, againconnected to my work at the
(12:36):
Dutch Brain man, looked at allthe transcriptional profiles and
the whole genome way toidentify hub genes.
That would explain why thedisease actually develops and
how it would potentially treatit.
I also realized we need atranslational model so that we
can test therapeutics and testhypotheses and did the same with
(13:00):
all of the animal models thatwere published, all of the
transcription data sets from allof the different ALS models
that were published.
So I built this wholemeta-analysis of human and
animal post-mortem tissue to seeif I could find things that
were conserved between the twomodel systems Zero overlap.
(13:20):
I was incredibly frustratedbecause we have the genetics, we
know what's gone wrong inpatients, we can probably
develop therapeutics, but wehave no way to test it.
How do we test this?
And then I discovered KevinHagen's work, who was at Harvard
and had taken skin cells from apatient, together with this
collaborator at Mass GeneralHospital, james Berry, and he
(13:44):
had used the Yamanaka protocolsto turn drugs into stem cells.
And he's a developmentalbiologist by training and knew
how to make motor neurons fromstem cells, and so he was able
to create motor neurons frompatients, and so the same
neurons that are dying in apatient's spinal cord it would
recreate from a skin cell andstudy.
And so I thought this isphenomenal.
(14:05):
That must translate.
If we can see what has gonewrong in a patient's own cells,
in the cells that are dying intheir disease, and we can test
potential therapeutics, then itmust be translating again back
to patients and so I decided toquit my job at J&J.
I looked up Kevin.
I was collaborating withClifford Wolfe, another
professor, the head of theneurobiology center at
(14:28):
Children's Hospital, and I saidcan I please work with you
Because I want to learn thistechnology stem cell technology
which was super controversial atthat time.
They liked my industrybackground.
They had a collaboration withGSK.
I had no one in their labs whoactually knew how to work with
pharma companies, so it kind oflike was a good match.
And then for three years Iworked together with them
(14:50):
learned everything.
I wanted to know about theseneuronal model systems.
And then I decided I'm done,I'm going to start my company.
And so I told Kevin and my planwas to go back to Europe to do
that.
So I told Kevin.
I'm like thank you so much,it's been incredibly great
experience.
I'm going to start an ALScompany.
(15:11):
And I talked to him about thatbefore and he said, oh, maybe we
can do something together.
And I never really took himserious.
He was a hard professor.
But then he said, well, let'sdo that together.
And let's do it here.
Let me introduce you to somepeople who might be interested
in being part of that, and thatactually led to the creation of
(15:32):
Curalis, and both Kevin andClifford became co-founders,
together with myself and the CEOof another company that Kevin
started, jonathan Fleming, whoused to be a managing partner at
Oxford Biosciences.
He decided to be part of thatas well, and we created Curalis
to develop precisiontherapeutics for ATLAS based on
(15:53):
the insight derived from thesepatient-derived disease models,
and so the first two bigdiscoveries that were made are
now in the clinic.
Those are our first clinicalprograms.
Ben Comer (16:03):
I had just a follow-up on J&J.
Is Curalis, a member of J-Labs,part of the incubator there?
Yes, and what sort of benefitscome along with that?
What's your experience withthat program?
Matt Pillar (16:18):
I think J&J has J-Labs to get close access to
new and exciting technologies.
Kasper Roet (16:27):
So you know Q-State started.
Matt Pillar (16:31):
So the company where Jonathan worked was called
Q-State and Q-State was foundedout of Q-State.
So Q-State was kind of helpingget Q-State established.
The first office that I had wasbasically a closet in Q-State.
It's like a little room in themiddle of the building without
any windows.
My wife bought me a plant.
(16:52):
The plant was the real employeeof the office, but you know, we
were raising a little bit ofseed money and then someone
advised me to apply for a goldenticket with Amgen to get access
to Lab Central.
Lab Central is one of the maybethe foremost bio-incubator space
(17:13):
in the world.
It's like in the middle ofKendall Square, 700 Main Street,
started by Johannes Brughaaf,and I won Kira was one won the
MJ Golden Ticket.
They have a ticket like this,big like a piece of cardboard,
but it gave me access toLabCentral and I actually didn't
(17:36):
know what it was until I gotthere.
Jlab is a sponsor of LabCentraland so our office that we got
at LabCentral was right next toJLab's office and so suddenly we
had this and then we became aJLab member.
You know we applied and we wantthat as well, but what you then
get is a very close vicinity toa large pharmaceutical company
(17:59):
and the people that areinterested in new technologies.
We were bringing precisiontherapies based on central
technology, which is a very newtechnology.
At that time J&J was veryinterested in that.
The other company that wasright next to that was Roche.
They also had an office rightnext to us, and so that is one
of these amazing things that youhave in Kendall Square.
(18:20):
It's just close to all of thesecompanies, and we won another
golden ticket from Pfizer, gotanother year of extension at
LabCentral.
But it's really the proximityof small companies to large
companies which makes Cambridgeand Massachusetts such an
exciting environment.
Basically, labcentral is kindof the pinnacle of all of that,
because that's where it all kindof comes together in a very
(18:42):
close density.
Where's the company located now?
So at some point when we werestarting to close our Series A,
it was time for us to get morespace.
I wanted to stay in Kendallbecause I liked the buzz, but my
team set Casper to commute toKendall.
(19:04):
It's really painful for us.
We live outside of the city.
It takes us half an hour justto be in Cambridge and half an
hour back if it's a good day, soI can get a little bit further
away.
So I said, fine, we're going tostay in Cambridge.
So we are now behind the ILLWACstation in West Cambridge.
There's a little biotech hubthere as well.
Gsk sits there, ucb sits there,a-side sits there A bunch of
(19:30):
little companies.
It's actually quite a nice, alittle small company.
Kasper Roet (19:43):
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(20:06):
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Alston and Bird represents lifesciences companies and their
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(20:28):
product development, frompreclinical to post-approval
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Learn more at Alstoncom andtell them you learned about them
.
On the business of biotech, Iwant to talk a little bit about
the regulatory scene in thespace that you're in.
You just mentioned yourclinical programs and we'll get
(20:49):
into that a little bit moredeeply later on in the
conversation.
But being in a space that's notsuper well charted from a
regulatory standpoint, what'sbeen your experience with the
regulators as you've moved thoseprograms into the clinic?
Matt Pillar (21:05):
Yeah, our experience with the regulators
overall has been good, but we'venoticed that the FDA has a kind
of on the genetic medicineswhere our programs kind of fall,
specifically the RNAtherapeutics, and the FDA has a
very conservative approach tothat, very much focused on risk,
(21:30):
much less focused on benefit,and so that has basically driven
us to start our clinical workoutside of the United States.
So Curalis is running programs.
We have now three programs.
They're running in sixdifferent countries in Canada,
the UK, belgium, netherlands,ireland and Germany and not in
(21:53):
the US.
And then we found out that alot of other companies are doing
the exact same thing.
And when I started to talkaround and like are we the only
people that think that weshouldn't start in the US, we
actually found out that almostevery company that we talked to
has that opinion because itcreates just a regulatory risk
(22:18):
and a hurdle.
And why would you take that,basically, if you don't have to?
And so we've brought together aconsortium of companies it's
now 11 companies with we as akind of the founding members of
Curalis Stokes Therapeutics,avivity, bio, ultragenyx and we
(22:41):
brought together other companiesto really try to catalyze
changes and work with the FDA tosee if we can build more of a
risk-benefit approach into theregulatory pathway.
So I think the SEA in particularhas done a lot of really good
things on the back end.
(23:02):
Trying to get to certainendpoints biomarkers and
Alzheimer's has been aremarkable step forward there,
with amyloid in ALS, where weare currently with our programs,
a big step forward because ofneurofilament for the SOD1
population.
So I think there's been a bigdevelopment and evolution in a
(23:27):
positive way.
On getting trucks maybe fasterthrough the development pipeline
and maybe faster to anaccelerated approval.
But on the front end there'sbeen a very rigid system and so
we think that there should beimprovements there.
So we've made that from theconsortium.
(23:48):
We've made a case to the FDAwent to the Rare Disease Hub Day
which was organized in October.
I presented there, stokepresented there, avidity
presented there.
There were a number of othercompanies that were presenting
there as well, and we made itclear that we'd like to work
with the FDA because they madethis important step on creating
(24:09):
a Rare Disease Hub to see ifthere could be ways in which we
can also smooth this process,because at this moment American
innovation is basically leavingthe United States and it's not
benefiting American patients andthat is kind of our broking
system.
Ben Comer (24:25):
Is it your feeling that the regulators have been
open to listening andcollaborating with you?
Do you feel like you've beenable to move the needle as a
company?
Matt Pillar (24:34):
Yes, I think you know there are differences also
in the way CBER and CEDARoperate, but Peter Marks was
there, patricia Capazzoni wasthere and I was able to connect
with both of them and you don'thave commitments, they're right
there on the spot.
(24:55):
But there was definitely apositive attitude and an
understanding that this wasn'tthe first time that they heard
about it, like other companieshave, but this is the first time
that I think the companies havekind of united and I know the
large pharmaceutical companieshave the exact same few points
because I talked to all of them,because we're all working
(25:16):
together.
But there's definitely anunderstanding and there was an
appreciation and a willingness,I think, to make improvements,
and so the FDA has then put outa call to get written feedback
and then recently also put out acall for all of the nucleotide
therapies on what could be animprovement for the regulatory
(25:38):
framework and, again on behalfof the consortium, we have
provided that and that was justsubmitted like two days ago, and
so it all takes time, but Ithink there is a.
There is definitely uh, thereare things moving in a hopefully
in a positive direction.
But obviously Rob Caleb steppeddown, so we're going to get a
(25:58):
new commissioner Patricia justannounced to step down, so we
also have to see what who'sgoing to be there to work with.
So hopefully that will notcreate too much chaos, that we
can continue to move, yeah.
Kasper Roet (26:13):
I was going to ask where you feel I mean, it sounds
like there's a concerted effortthat, uh, I guess to continue
to apply not not pressure butinfluence, um, and I was gonna
ask where, where perhaps youfeel as though influence is is
limited or metered, like wheremore work needs to be done, but
it sounds like that's kind oftbD, depending on some
administrative positioning.
Matt Pillar (26:34):
I think so.
Yeah, I mean I knew Rob wasgoing to leave, but the KHS
departure, I think, was asurprise to everyone, and so now
we're going to have to see whatwe should work with.
But I think the reason why it'sso important is that this is
(26:56):
the time of genetic medicine,this is the time of RNA
therapeutics.
You can see a lot of differentcompanies active in this space.
The genetic insights intodisease the thing that got me
interested to develop therapiesfor ALS, because the genetics
gives us a real handle on how totreat this disease.
The best way to do that isprobably through genetic
(27:17):
medicine, because the two kindof link very nicely together.
But you have to have adifferent approach to that than
you have for small molecules orantibodies, and so there's a
real need, I think, for us toall evolve rapidly with these
new technologies and also from aregulatory side, and so we will
(27:38):
continue to communicate thatvery strongly to the FDA and
whoever will be the new leadersof CEDAR and the FDA themselves,
because there's no time to lose.
Ben Comer (27:50):
Basically, yeah, you're an admitted optimist.
How realistic do you thinkinteragency collaboration is and
greater harmonization?
Matt Pillar (28:01):
Well, I think you know, harmonization can be good,
but harmonization can also bebad.
It depends on you know whichwho's harmonizing.
Kasper Roet (28:12):
What part of harmony are we discussing here?
Matt Pillar (28:16):
But you know there are a lot of things I don't
completely understand.
I know that the EMA and the FDAare connecting Health Canada,
the NHRA, but there's a lot ofalso higher level conversations.
The experiences that we've hadwith Q-RALIS is that regulators
in different countries have adifferent way of looking at
(28:37):
things, and so I think that'sfine.
And you know, maybe it's goodthat I'm a big believer in group
thinking and the diversity ofopinions.
It's also good if theycommunicate a lot so that they
can learn from each other.
But I'm mostly an optimistbecause I believe that everyone
wants the same thing.
(28:58):
Like everyone has familymembers who have been sick or
who have passed away, or you'reafraid of family members or
friends getting sick or passingaway, we all want medicine.
We all want to have treatmentsfor diseases.
I've met so many people nowthat have ALS or have passed
(29:18):
away from ALS, or have familymembers or friends that have the
disease, and that's just onedisease, right, it's the same in
oncology, it's the same inepilepsy, you name it.
Everyone wants treatments andso if you use that, then we
should all be able to findcommon grounds to do the right
things and to make a frameworkthat supports therapy
(29:40):
development.
So I'm very optimistic becauseI think it's common sense.
I don't know why anyonewouldn't want to do that.
Ben Comer (29:47):
Well, and I think ALS has one of the more active
patient advocacy communities.
That wasn't the original icebucket challenge around ALS.
Does that help you in your roleat Ecuralis?
Matt Pillar (30:02):
Yes, the Ice Bucket Challenge was really created by
Pete Frates and the ALSAssociation has really lifted
that, I think, to a globalawareness.
It has been incrediblyimportant for ALS because I
think most people had not evenheard of the disease before the
Ice Bucket Challenge.
Now everyone knows about thedisease.
(30:23):
It has also brought a lot ofmoney to the foundation and to
other organizations, and one ofmy fellowships when I was
working at Harvard was from theALS Association.
So you know, in a way, theresearch that has also led to
the creation of Q-RALIS is, Ithink, directly supported by
(30:44):
money from the IcebreakerChallenge, Milton
Safenov-Richfield.
So, yes, I think that type ofawareness and that action has
been incredibly important andthat action has been incredibly
important.
Kasper Roet (31:00):
You referenced this , I guess the risk of the exodus
of clinical activity andinnovation away from the FDA
because there are lower barriersand other perhaps lower
(31:20):
barriers and other regulatoryjurisdictions.
That's to say, you didn't evenmention Australia, which has
been one of the major sort ofsiphons of clinical activity
away from the US.
What would you call on thespace to do, like you've been
like, admirably active incalling for and influencing
change?
What would you call on the restof the space to do, like?
(31:41):
What levers might they have topush and pull to join the effort
?
Do you see enough activitygoing on in the greater
landscape.
Matt Pillar (31:51):
Once you start doing these things, you notice
how many other companies aredoing that.
I think the weakness is thatcompanies advocate for
themselves a lot and don't uniteenough to have a united message
.
Because if one company goes andis lobbying for, in this case,
(32:15):
the FDA to look at its ownprocesses, it feels like that
company is just trying to helpthemselves and no one likes that
, because that just feels kindof like it doesn't feel good.
It's like you're trying to skewthe system in your own benefit,
but that's not what we'retrying to do.
There's definitely somethingnot working in the system and
(32:38):
the fixing that will benefiteveryone, and so we've done a
lot of background conversationsalso with companies that maybe
don't want to publicly be partof a consortium, but that we
have the same message so thatthe same message is being heard
over and over and over again.
So because, in the end, if yougive 10 different messages to
(32:59):
someone, they can't remember anyof this.
Right?
I think someone remembers maybethree things very well.
So you want to make sure thatyou have your priorities
straight as a whole biotechsector and then you you give the
same message that, even if itis not part of our consortium,
but an independent message, andso that is something that we've
(33:20):
been doing also with theconsortium, and talked to all of
the large pharma companies thatare active in the ALS space,
and we're all aligned, so it'simportant that we work in that
manner.
Ben Comer (33:32):
Basically, yeah, maybe we can turn it back to
Kira Alice's development andclinical assets right now.
Could you give us a sense ofwhere you are and maybe what
your next big milestones orgoals are with your clinical
programs?
Matt Pillar (33:53):
Yes, I'd be very happy to and just maybe want to
also explain where your clinicalprograms come from.
So the first big discovery thatwas made using patient stem
cells, which were then generatedinto neurons, was that there's
a loss of a potassium channelcalled KD7.2.
(34:15):
The loss of that potassiumchannel leads to neuronal death
in these stem cell models and soif you activate that potassium
channel you can protect againstthat.
We found out it's misplaced.
It's pre-mRNA includes askeptic exon which turns it into
a protein which is rapidlydegraded again, leading to
(34:38):
neuronal death.
But you can protect againstthat with a KD7 opener.
So that is something that wehave now brought to the clinic
and that program is currently atthe end of its phase one.
We've actually run threestudies, four studies in
parallel a MAD study, a multipleascending dose study to look at
(34:58):
tolerability of courseincredibly important.
We've also run a healthyvolunteer study to look at
biomarkers that predict survivalfor ALS but also for epilepsy,
to look at biomarkers thatpredict efficacy in epilepsy,
because the potassium channelsare very important for epilepsy.
We ran a PK study to look atthe three different formulations
(35:21):
, to see which formulationswould be best for these
different indications, and we'vealso ran a patient study to see
how this compound works inpatients.
Most of that data is reading nowto the end of this quarter, and
so this is an incrediblyimportant quarter for us, and so
we're very excited aboutlooking at the results.
Then we have the second bigdiscovery that was made, again
(35:46):
from my co-founder was the lossof our staph-2 micro tubules,
stabilizing protein essentialfor the innervation of your
muscle, so your motor neuronsprotect from your spinal cord
all the way to your muscles, forinstance in your hands and in
your feet.
That innervation is lost whenthere's a loss of staph in tube.
What Kevin discovered is thatit's driven by a mis-splicing
(36:08):
event, and when we realized thatit was just after SpingRoss.
It was approved for spinalmuscular atrophy, a splice
correction ASO targeting motorneurons in the spinal cords of
estimated patients, showingremarkable effects in those
patients.
Really transforming therapythat is marketed by BioChip has
helped so many differentpatients.
We thought we can do that alsofor restoring staph in two
(36:35):
levels and bringing staph in twolevels back to normal, which
again is lost in almost everyALS patient.
At this moment we're running adose range finding trial in six
different countries wherepatients are dose-free for D-glu
that have injections into theirspinal cord with an ASO, an
incisor oligonucleotide thatrestores these staph name levels
, and we are now basicallyexpanding on two different dose
(36:57):
levels to see which of thesedose levels is going to be
effective for following patientsfor an extended period of time.
We're looking at biomarkersthat predict efficacy,
neurofilament and compact muscleaction potential, which
measures this innervation, andwe're going to read that out in
the first half of next year.
Ben Comer (37:17):
And what phase are you in on your clinical trials
with those two?
Matt Pillar (37:20):
So I would say that it's now in a phase two phase,
but with these programs you kindof adapt from phase one to
phase two.
With the KV7, we're at the endof phase one and we're planning
to start phase two trials at theend of the year.
Ben Comer (37:38):
With the KV7 opener, which prevents the potassium
channel from shutting down,which then prevents the neuronal
death?
Does that have to beadministered very early on after
diagnosis of ALS, or when doyou have to catch the patient to
?
Matt Pillar (37:54):
prevent that from closing.
Ben Comer (37:55):
Yeah, that's a great question.
Kasper Roet (37:57):
So ALS is a progressive neurodegenerative
disease.
Matt Pillar (38:00):
So ALS is a progressive neurodegenerative
disease and so other than, forinstance, parkinson's, where if
you have symptoms you've lostalmost all of your dopaminergic
neurons, so there's not a lot toactually protect it.
Still, in ALS, when people havedeveloped symptoms, they still
have a lot of their motorneurons and so over time there's
motor neurons that are stillhealthy, there's motor neurons
(38:22):
that are sick and there's motorneurons that have died, and so
obviously at the end of thedisease a lot of neurons have
died, but at the beginning not.
So in essence you can treatanywhere and have an impact on
the disease.
But in reality the earlier youtreat, the bigger impact you
will have on preventing loss offunction.
So the earlier you treat, thebigger impact you will have on
preventing loss of function.
(38:43):
So the earlier you treat, thebetter you are at picking up
effects of a potentialtherapeutic.
And so early treatment I think,has become kind of a norm for
all neurodegenerative diseases,not because the therapies don't
work if you treat later, butjust because that's where you
have the biggest impact on thedisease.
Kasper Roet (39:03):
We're going to run short on time here, so just a
few more questions and thenwe'll chat.
I talked too much, no, no, no,you're doing great, terrific
responses.
It's been a super meaningfulconversation.
I like the global aspect of it,but in keeping with progress at
Curalis, you mentioned that youwere one of the fortunate
companies to have a presentationat JPMorgan.
There are so many biotechs herewho don't have opportunities to
(39:25):
present at the conference.
They're here for the ancillaryactivity.
How did that go?
Matt Pillar (39:33):
It was a great honor to be invited as a private
company to present at theJPMorgan conference.
I thought it was a greatsuccess.
Kasper Roet (39:44):
I didn't anticipate that you would tell me oh, it
was awful man, I mean it, justit spiraled yeah.
Matt Pillar (39:50):
Oh, we got some good questions back also because
there have been failures in theAOS space and how do we look at
that?
And yeah, I don't want to go toodeep into it, but the
traditional approach ofcompanies has just been looking
at mechanisms that may play arole in disease and then having
a compound, or usually a smallmolecule, that acts on that
(40:11):
mechanism and then hoping thatit does something.
We're following it really froma genetic approach.
So we actually have.
We're the leading company inthe development of therapeutics
for ALS because we have threeprograms in development on
genetic targets the.
The last one, on 13, ispartnered with eli still
pre-clinical, but it's thisgenetic approach that we know
(40:32):
works, and so I've been tryingto educate that to people and uh
, and so this was a questionthat we got also at the JP
Morgan conference.
Just want to give you a littlebit more information on that at
Baltimore.
Kasper Roet (40:47):
Yeah Well, I was going to ask you and hopefully
this will answer the question,because we spoke like a week or
so ago.
Two weeks ago, we had theopportunity to chit chat with
you about what we're going totalk about today and I remember
you saying specifically like weknow it works, we have the tools
, and you said now we just needto do it.
So hopefully that question isgoing to be answered.
(41:08):
What's going on right now interms of all right we're going
to go from we know it works, nowwe just need to do it?
Matt Pillar (41:13):
Yeah, so the first gene that was discovered for ALS
is SOD1.
And that was discovered in 1993.
It was approved in 2023.
So it took 30 years to getthrough an approval.
At this moment, if weunderstand what is going wrong
(41:34):
in the genetics of a disease, wecan be in the clinic four years
later with a genetic medicine.
The path from a geneticdiscovery to a development
candidate, to an IND, to a POC,is a scalable path with these
genetic medicines, specificallyfor RNA therapeutics, and so
that is very powerful, becausegenetics makes us understand why
(41:57):
someone gets sick not for everydisease, but for a lot of
diseases.
Kasper Roet (42:01):
We understand the genetics.
Matt Pillar (42:03):
We have now the technology to build that into a
medicine relatively quickly in avery reproducible manner, and
so we have now done.
At Curalis.
We've made four developmentcandidates.
We know exactly how long thattakes.
We know exactly how to do theseAD&D enabling studies.
We've done that multiple timesas well, and we now have also
(42:24):
learned how to actually run POCprograms.
That's not just for ALS right,but there's many other diseases
where that can be done.
And again that comes back againon why we need also a
regulatory framework that fitswith that, because I think as a
humanity you heard me say thisin the beginning no one wants to
(42:44):
be sick.
No one wants their friends andfamily members to be sick.
We have an opportunity to makereally meaningful therapeutics
for many different people in avery fast way relatively to the
past and in a very highprobability for the success type
of matter.
But so we need to do it, yeah.
Ben Comer (43:09):
That's Curalis.
Founder and CEO of Casper Root.
I'm Ben Fommer, very nice.
Kasper Roet (43:14):
And I'm Matt Feller .
You did a much better job.
Ben Comer (43:16):
Oh, thank you, and you just listened to the
Business of Biotech from JPM2025.
Listen and subscribe whereveryou listen to podcasts or take
our video cast in at BioprocessOnline and Life Science Leader.
Thanks for listening and seeyou next week.
There's not much metering.
Kasper Roet's confidence in hiscompany's technology can
counter neurological disorderslike ALS.
If his long-standing andhands-on commitment to neuro
research is any indication thatconfidence is well placed.
I'm Ben Comer and I'm MattPillar and this is the Business
of Biotech JPMorgan 2025 edition, and we're here in San
(00:26):
Francisco at the law offices ofAlston & Bird with Dr
Roet, founder and.
Ceo of QurAlis, to explore thewhy behind his optimism.
Dr Roet, thanks for being here.
Matt Pillar (00:38):
My pleasure.
Thanks for inviting me.
Kasper Roet (00:40):
It's our pleasure, dr Root, and I noticed you
rolled the R on the firstpronunciation and then rolled
right back into the straight.
Ben Comer (00:47):
American.
Yeah, you know, I tried it andI thought it sounded a little
funny coming out of my mouth.
I need to practice it some morebefore I pull it back out.
Kasper Roet (00:53):
I give you kudos for even trying.
I appreciate that.
So you've got a very diverseand hands-on background in
pretty much everything thatyou've done hands-on background
in pretty much everything thatyou've done.
And I'm curious about thebeginnings of your career.
Before you got into lifesciences, you started your
career in IT.
Is that correct?
Matt Pillar (01:11):
That is correct.
Kasper Roet (01:13):
So tell us a little bit about that and where, when
and why the pivot from IT intolife sciences occurred.
Matt Pillar (01:23):
My IT life comes from the fact that I have a
passion for computers.
I started that as a very youngchild and when the internet boom
started in the 1990s, I was oneof the few people that knew how
to assemble computers, takethem apart, program them, build
Wi-Fi networks.
And so when I was finishing mybachelor degree at the
(01:47):
University of Amsterdam, me andtwo friends were asked to help
with small companies and studenthouses to set up their IT
infrastructure so that everyonecould get access to the internet
.
So I kind of rolled that into acompany and that became
actually an IT company thatfirst built infrastructure, then
built web applications and thenalso placed IT specialists at
(02:10):
other companies to solve theirproblems.
I had never anticipated beingan entrepreneur before that.
It was kind of a naturalevolution to become an
entrepreneur, and when Irealized how great it was to
actually be able to create yourown visions into reality, I was
caught and I knew I wanted to bean entrepreneur.
Kasper Roet (02:30):
But I also knew.
Matt Pillar (02:31):
I didn't actually want to be an IT entrepreneur
it's my passion.
I've always been on biology andI really wanted to develop
medicine so that we couldactually have a world hopefully
a future world where we don'tsuffer from diseases anymore.
Kasper Roet (02:46):
Yeah Well, let me just say that I think you made
the right choice because yourpersonality lends itself to
medicine.
I covered IT for like 20 yearsand the IT space.
The people that I interviewedin the IT space not nearly as
chill.
As you are right, there'sbigger egos in the IT space than
there are in the life sciences,and so I think you made the
(03:08):
right decision.
Based on what I know about youso far, Good.
Matt Pillar (03:12):
What was your first computer?
My first computer.
You know like I had a Commodore64, but I actually had like a
games computer before that.
I don't think I must haveexplored it with a Comm computer
anymore, but I think that well,I guess I'm an Atari before the
Commodore.
That's like evolved and youtook all this apart.
(03:32):
Yes, I always tried to makethem a little faster and crank
up their memory a little bit soI could play better games.
That was really the bigmotivator, yeah.
Kasper Roet (03:42):
What was your foray when you decided that you
wanted to pursue something inthe life sciences medicine
related?
What was your first foray intothat field?
Matt Pillar (03:53):
My first foray.
You know, I started actuallywith artificial intelligence in
my university track.
But I come from the fields of asmall farm town.
Actually, the first lake thatwas dried out the big lake in
the Netherlands was where I grewup and I had a microscope and I
(04:16):
caught little bugs in the fieldand I was just taking them
apart to see how they work.
And that was really a passionfor me, and not just thinking
the box, but understandingbiology and understanding nature
.
And so I was doing thisartificial intelligence.
But I realized a lot of peopleare probably better at
programming and I realized Ishould just do what I'm really
(04:39):
good at and I decided to studymedical biology again at the
University of Amsterdam and Iloved it the moment I started
that I was just in love with it.
And then after that I enrolledin this IT company.
But I went back and did amaster's in neuroscience and
there I was working in one ofthe former gene therapy labs in
(05:02):
the Netherlands.
The lab of Joost Verhagen wasreally pushing gene therapy
technologies forward.
Because I wanted to translate.
At that moment I already knew Iwanted to make medicine and
gene therapy is actually anultimate medicine and that kind
of got me the exposure in theneuroscience space, because that
(05:24):
is where Yoast was working tomake gene therapies for spinal
cord repair, for paralyzedpeople, and so I did my master's
internship there.
I did a master's internship inUCSD with Mark Trushinsky, a big
gene therapy scientist there,and then I came back to do a PhD
(05:44):
.
But again I wanted to dosomething that was really
translational.
So I started a gene therapy PhDproject which was a
collaboration between theUniversity of Amsterdam, the
Free University, a&t, which wasAmsterdam Molecular Therapeutics
, which later became Unicure,quite a successful gene therapy
company.
(06:04):
At that time they actuallybrought the first gene therapy
into the Western markets forKlaipera, and so I was there at
that time while they were doingthat and I was also
collaborating with Galapagos.
They were part of the project.
Basically it was called theCenter Nolten Project, again to
bring gene therapies to spinalcord repair.
Basically it was called thesensor nolten project, again to
(06:26):
bring gene therapies to spinalcord repair.
And so the institute where Iworked, the nebulous institute
for neuroscience, was actually,um, the.
The director there started thedutch brain bank and the dutch
brain bank is one of I think oneof the best brain banks in the
world, because usually withintwo hours after a donor passes
away, the body is brought to thehospital and we're following an
(06:50):
autopsy protocol to take outbrain and spinal cord and
process that in a certain way,depending on the disease.
And I started to work there andbecame an autopsy coordinator,
which meant that in the middleof the night I would get a phone
call someone has passed away.
Can you please organize theautopsy?
(07:12):
So I would call the families, Iwould call the undertaker, I
would call the neuropathologist,the section assistant, we would
all go to the hospital, wewould receive the body, we would
then look at it and I could seethe impact that all these
neurodegenerative diseases haveon patients talking to their
family, looking at their bodies,looking at their brains,
(07:32):
looking at their spinal cords,taking it apart and sometimes
bringing the tissues back to theinstitute where, sometimes in
the middle of the night,researchers would come to try to
find out things that werehappening in those diseases.
And that really caught me intothe broader neurodegenerative
space.
And so, yeah, that is whatreally started to motivate me,
(07:56):
just the incredible impact thatthose diseases have on those
patients, both on them obviouslythey've passed away at that
point but also on their familiesat that point, but also on
their families and I decided Ido and really specialize in
development of therapies forneurodegenerative diseases.
Ben Comer (08:11):
How did that really hands-on experience at the
Netherlands Brain Bank influenceyour career and where you are
now?
Because that strikes me asunique.
Not everyone in the industryhas that degree of you know
handling a brain that works inneuroscience.
Matt Pillar (08:29):
Yeah, I can tell you it's really helpful right
now because we're working on anautopsy program for our current
trial and I understand how itworks, what it means to have
tissue, how it's processed youknow I'm the CEO, but it's good
to have that type ofunderstanding.
And you know my company is nowcollaborating with the Dutch
(08:51):
Brain Bank.
We just started a program alsofor Fragile X.
We wanted to get tissue fromFragile X patients and the
tissue that we got from thesepatients we've been able to
study and really confirm agenetic target for Fragile X.
I mean that has really helpedme to appreciate the tissue and
really confirm a genetic targetfor Fragile X.
I mean that has really helpedme to appreciate the tissue.
(09:11):
One of the other things that Ireally took away from that is
how often patients aremisdiagnosed, because clinicians
misdiagnose patients based onclinical symptoms.
But once you open up someone'sbody and you look actually on
how the disease looks inside thebody, very often we saw that
the clinical diagnosis was notcorrect.
But a clinical diagnosis oftenstands and so when you get
(09:35):
tissue from a donor, theclinical diagnosis is the
diagnosis.
You have to really read throughthat to see if the pathological
diagnosis is the same, becauseotherwise you're actually
drawing the wrong conclusions onthe materials that you use.
And that's a very practicalpoint where my experience there
has really given me caution oninterpretation of data from
(09:58):
material from donors, and Ithink it's helping us do better
things in Curalis, yeah, and Ithink it's helping us do better
things in Curalis.
Kasper Roet (10:07):
Yeah, so we kind of fast-forwarded to Curalis.
There were a couple of stopsbetween the Dutch Brain Bank and
your founding of Curalis.
Matt Pillar (10:15):
Yeah, again, I knew I wanted to develop medicine
and I realized I know how a lotof companies worked.
I worked as a computerspecialist in a computer company
as a side job.
I was a telephone marketer fora while.
I worked at an investment bank,and so I kind of knew a lot of
(10:38):
different sectors.
Kasper Roet (10:39):
Worked in a bar.
Had no idea how you make atruck.
Matt Pillar (10:42):
And it's like I want to start a company
developing therapeutics, Ireally need to understand how to
make a truck.
And so in the Netherlands oneof the big R&D organizations at
that moment was J&J, who hadtheir Janssen vaccine site there
which was formerly Crucell butwas acquired by J&J just before
(11:04):
that time that I graduated withmy PhD and I applied there and
got a job, first as an assaypotency development team leader
and that kind of progressed intobecoming a technical integrator
and there I learned how you getsomething from research all the
(11:24):
way to the clinic, because Iworked together with Formulation
, phil and ThinHash upstreamprocessing, downstream
processing, clinical assays, qcassays, r&d, cmc, and there, a
couple of years in, I reallyunderstood how you can actually
make a drug and how thepharmaceutical business works
and what type of experts youneed and all of that.
(11:45):
And while I was doing thatC9-472 was discovered big ALS
gene.
My PhD program was spinal cordrepair, gene therapies.
So neuromuscular ALS is aneuromuscular disease and so
it's the same tissues.
But I thought we cannot treatALS because we don't understand
the disease.
Kasper Roet (12:05):
But while I was at JMJ, a big ALS gene was
discovered and then rapidly, 300ALS genes were discovered.
Matt Pillar (12:13):
And I'm a big data person, probably because of my
passion for computers, and so Istarted looking at that and I
thought this is incredible.
We have the genetics of thedisease.
I could see pathways emerge.
I could see this is incredible.
We have the genetics of thedisease, I could see pathways
emerge.
I could see disease mechanismsemerge.
And so in my hobby time I tookpublished data sets from
post-mortem tissues, againconnected to my work at the
(12:36):
Dutch Brain man, looked at allthe transcriptional profiles and
the whole genome way toidentify hub genes.
That would explain why thedisease actually develops and
how it would potentially treatit.
I also realized we need atranslational model so that we
can test therapeutics and testhypotheses and did the same with
(13:00):
all of the animal models thatwere published, all of the
transcription data sets from allof the different ALS models
that were published.
So I built this wholemeta-analysis of human and
animal post-mortem tissue to seeif I could find things that
were conserved between the twomodel systems Zero overlap.
(13:20):
I was incredibly frustratedbecause we have the genetics, we
know what's gone wrong inpatients, we can probably
develop therapeutics, but wehave no way to test it.
How do we test this?
And then I discovered KevinHagen's work, who was at Harvard
and had taken skin cells from apatient, together with this
collaborator at Mass GeneralHospital, james Berry, and he
(13:44):
had used the Yamanaka protocolsto turn drugs into stem cells.
And he's a developmentalbiologist by training and knew
how to make motor neurons fromstem cells, and so he was able
to create motor neurons frompatients, and so the same
neurons that are dying in apatient's spinal cord it would
recreate from a skin cell andstudy.
And so I thought this isphenomenal.
(14:05):
That must translate.
If we can see what has gonewrong in a patient's own cells,
in the cells that are dying intheir disease, and we can test
potential therapeutics, then itmust be translating again back
to patients and so I decided toquit my job at J&J.
I looked up Kevin.
I was collaborating withClifford Wolfe, another
professor, the head of theneurobiology center at
(14:28):
Children's Hospital, and I saidcan I please work with you
Because I want to learn thistechnology stem cell technology
which was super controversial atthat time.
They liked my industrybackground.
They had a collaboration withGSK.
I had no one in their labs whoactually knew how to work with
pharma companies, so it kind oflike was a good match.
And then for three years Iworked together with them
(14:50):
learned everything.
I wanted to know about theseneuronal model systems.
And then I decided I'm done,I'm going to start my company.
And so I told Kevin and my planwas to go back to Europe to do
that.
So I told Kevin.
I'm like thank you so much,it's been incredibly great
experience.
I'm going to start an ALScompany.
(15:11):
And I talked to him about thatbefore and he said, oh, maybe we
can do something together.
And I never really took himserious.
He was a hard professor.
But then he said, well, let'sdo that together.
And let's do it here.
Let me introduce you to somepeople who might be interested
in being part of that, and thatactually led to the creation of
(15:32):
Curalis, and both Kevin andClifford became co-founders,
together with myself and the CEOof another company that Kevin
started, jonathan Fleming, whoused to be a managing partner at
Oxford Biosciences.
He decided to be part of thatas well, and we created Curalis
to develop precisiontherapeutics for ATLAS based on
(15:53):
the insight derived from thesepatient-derived disease models,
and so the first two bigdiscoveries that were made are
now in the clinic.
Those are our first clinicalprograms.
Ben Comer (16:03):
I had just a follow-up on J&J.
Is Curalis, a member of J-Labs,part of the incubator there?
Yes, and what sort of benefitscome along with that?
What's your experience withthat program?
Matt Pillar (16:18):
I think J&J has J-Labs to get close access to
new and exciting technologies.
Kasper Roet (16:27):
So you know Q-State started.
Matt Pillar (16:31):
So the company where Jonathan worked was called
Q-State and Q-State was foundedout of Q-State.
So Q-State was kind of helpingget Q-State established.
The first office that I had wasbasically a closet in Q-State.
It's like a little room in themiddle of the building without
any windows.
My wife bought me a plant.
(16:52):
The plant was the real employeeof the office, but you know, we
were raising a little bit ofseed money and then someone
advised me to apply for a goldenticket with Amgen to get access
to Lab Central.
Lab Central is one of the maybethe foremost bio-incubator space
(17:13):
in the world.
It's like in the middle ofKendall Square, 700 Main Street,
started by Johannes Brughaaf,and I won Kira was one won the
MJ Golden Ticket.
They have a ticket like this,big like a piece of cardboard,
but it gave me access toLabCentral and I actually didn't
(17:36):
know what it was until I gotthere.
Jlab is a sponsor of LabCentraland so our office that we got
at LabCentral was right next toJLab's office and so suddenly we
had this and then we became aJLab member.
You know we applied and we wantthat as well, but what you then
get is a very close vicinity toa large pharmaceutical company
(17:59):
and the people that areinterested in new technologies.
We were bringing precisiontherapies based on central
technology, which is a very newtechnology.
At that time J&J was veryinterested in that.
The other company that wasright next to that was Roche.
They also had an office rightnext to us, and so that is one
of these amazing things that youhave in Kendall Square.
(18:20):
It's just close to all of thesecompanies, and we won another
golden ticket from Pfizer, gotanother year of extension at
LabCentral.
But it's really the proximityof small companies to large
companies which makes Cambridgeand Massachusetts such an
exciting environment.
Basically, labcentral is kindof the pinnacle of all of that,
because that's where it all kindof comes together in a very
(18:42):
close density.
Where's the company located now?
So at some point when we werestarting to close our Series A,
it was time for us to get morespace.
I wanted to stay in Kendallbecause I liked the buzz, but my
team set Casper to commute toKendall.
(19:04):
It's really painful for us.
We live outside of the city.
It takes us half an hour justto be in Cambridge and half an
hour back if it's a good day, soI can get a little bit further
away.
So I said, fine, we're going tostay in Cambridge.
So we are now behind the ILLWACstation in West Cambridge.
There's a little biotech hubthere as well.
Gsk sits there, ucb sits there,a-side sits there A bunch of
(19:30):
little companies.
It's actually quite a nice, alittle small company.
Kasper Roet (19:43):
Our friends at Alston and Byrd set us up with
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product development, frompreclinical to post-approval
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Learn more at Alstoncom andtell them you learned about them
.
On the business of biotech, Iwant to talk a little bit about
the regulatory scene in thespace that you're in.
You just mentioned yourclinical programs and we'll get
(20:49):
into that a little bit moredeeply later on in the
conversation.
But being in a space that's notsuper well charted from a
regulatory standpoint, what'sbeen your experience with the
regulators as you've moved thoseprograms into the clinic?
Matt Pillar (21:05):
Yeah, our experience with the regulators
overall has been good, but we'venoticed that the FDA has a kind
of on the genetic medicineswhere our programs kind of fall,
specifically the RNAtherapeutics, and the FDA has a
very conservative approach tothat, very much focused on risk,
(21:30):
much less focused on benefit,and so that has basically driven
us to start our clinical workoutside of the United States.
So Curalis is running programs.
We have now three programs.
They're running in sixdifferent countries in Canada,
the UK, belgium, netherlands,ireland and Germany and not in
(21:53):
the US.
And then we found out that alot of other companies are doing
the exact same thing.
And when I started to talkaround and like are we the only
people that think that weshouldn't start in the US, we
actually found out that almostevery company that we talked to
has that opinion because itcreates just a regulatory risk
(22:18):
and a hurdle.
And why would you take that,basically, if you don't have to?
And so we've brought together aconsortium of companies it's
now 11 companies with we as akind of the founding members of
Curalis Stokes Therapeutics,avivity, bio, ultragenyx and we
(22:41):
brought together other companiesto really try to catalyze
changes and work with the FDA tosee if we can build more of a
risk-benefit approach into theregulatory pathway.
So I think the SEA in particularhas done a lot of really good
things on the back end.
(23:02):
Trying to get to certainendpoints biomarkers and
Alzheimer's has been aremarkable step forward there,
with amyloid in ALS, where weare currently with our programs,
a big step forward because ofneurofilament for the SOD1
population.
So I think there's been a bigdevelopment and evolution in a
(23:27):
positive way.
On getting trucks maybe fasterthrough the development pipeline
and maybe faster to anaccelerated approval.
But on the front end there'sbeen a very rigid system and so
we think that there should beimprovements there.
So we've made that from theconsortium.
(23:48):
We've made a case to the FDAwent to the Rare Disease Hub Day
which was organized in October.
I presented there, stokepresented there, avidity
presented there.
There were a number of othercompanies that were presenting
there as well, and we made itclear that we'd like to work
with the FDA because they madethis important step on creating
(24:09):
a Rare Disease Hub to see ifthere could be ways in which we
can also smooth this process,because at this moment American
innovation is basically leavingthe United States and it's not
benefiting American patients andthat is kind of our broking
system.
Ben Comer (24:25):
Is it your feeling that the regulators have been
open to listening andcollaborating with you?
Do you feel like you've beenable to move the needle as a
company?
Matt Pillar (24:34):
Yes, I think you know there are differences also
in the way CBER and CEDARoperate, but Peter Marks was
there, patricia Capazzoni wasthere and I was able to connect
with both of them and you don'thave commitments, they're right
there on the spot.
(24:55):
But there was definitely apositive attitude and an
understanding that this wasn'tthe first time that they heard
about it, like other companieshave, but this is the first time
that I think the companies havekind of united and I know the
large pharmaceutical companieshave the exact same few points
because I talked to all of them,because we're all working
(25:16):
together.
But there's definitely anunderstanding and there was an
appreciation and a willingness,I think, to make improvements,
and so the FDA has then put outa call to get written feedback
and then recently also put out acall for all of the nucleotide
therapies on what could be animprovement for the regulatory
(25:38):
framework and, again on behalfof the consortium, we have
provided that and that was justsubmitted like two days ago, and
so it all takes time, but Ithink there is a.
There is definitely uh, thereare things moving in a hopefully
in a positive direction.
But obviously Rob Caleb steppeddown, so we're going to get a
(25:58):
new commissioner Patricia justannounced to step down, so we
also have to see what who'sgoing to be there to work with.
So hopefully that will notcreate too much chaos, that we
can continue to move, yeah.
Kasper Roet (26:13):
I was going to ask where you feel I mean, it sounds
like there's a concerted effortthat, uh, I guess to continue
to apply not not pressure butinfluence, um, and I was gonna
ask where, where perhaps youfeel as though influence is is
limited or metered, like wheremore work needs to be done, but
it sounds like that's kind oftbD, depending on some
administrative positioning.
Matt Pillar (26:34):
I think so.
Yeah, I mean I knew Rob wasgoing to leave, but the KHS
departure, I think, was asurprise to everyone, and so now
we're going to have to see whatwe should work with.
But I think the reason why it'sso important is that this is
(26:56):
the time of genetic medicine,this is the time of RNA
therapeutics.
You can see a lot of differentcompanies active in this space.
The genetic insights intodisease the thing that got me
interested to develop therapiesfor ALS, because the genetics
gives us a real handle on how totreat this disease.
The best way to do that isprobably through genetic
(27:17):
medicine, because the two kindof link very nicely together.
But you have to have adifferent approach to that than
you have for small molecules orantibodies, and so there's a
real need, I think, for us toall evolve rapidly with these
new technologies and also from aregulatory side, and so we will
(27:38):
continue to communicate thatvery strongly to the FDA and
whoever will be the new leadersof CEDAR and the FDA themselves,
because there's no time to lose.
Ben Comer (27:50):
Basically, yeah, you're an admitted optimist.
How realistic do you thinkinteragency collaboration is and
greater harmonization?
Matt Pillar (28:01):
Well, I think you know, harmonization can be good,
but harmonization can also bebad.
It depends on you know whichwho's harmonizing.
Kasper Roet (28:12):
What part of harmony are we discussing here?
Matt Pillar (28:16):
But you know there are a lot of things I don't
completely understand.
I know that the EMA and the FDAare connecting Health Canada,
the NHRA, but there's a lot ofalso higher level conversations.
The experiences that we've hadwith Q-RALIS is that regulators
in different countries have adifferent way of looking at
(28:37):
things, and so I think that'sfine.
And you know, maybe it's goodthat I'm a big believer in group
thinking and the diversity ofopinions.
It's also good if theycommunicate a lot so that they
can learn from each other.
But I'm mostly an optimistbecause I believe that everyone
wants the same thing.
(28:58):
Like everyone has familymembers who have been sick or
who have passed away, or you'reafraid of family members or
friends getting sick or passingaway, we all want medicine.
We all want to have treatmentsfor diseases.
I've met so many people nowthat have ALS or have passed
(29:18):
away from ALS, or have familymembers or friends that have the
disease, and that's just onedisease, right, it's the same in
oncology, it's the same inepilepsy, you name it.
Everyone wants treatments andso if you use that, then we
should all be able to findcommon grounds to do the right
things and to make a frameworkthat supports therapy
(29:40):
development.
So I'm very optimistic becauseI think it's common sense.
I don't know why anyonewouldn't want to do that.
Ben Comer (29:47):
Well, and I think ALS has one of the more active
patient advocacy communities.
That wasn't the original icebucket challenge around ALS.
Does that help you in your roleat Ecuralis?
Matt Pillar (30:02):
Yes, the Ice Bucket Challenge was really created by
Pete Frates and the ALSAssociation has really lifted
that, I think, to a globalawareness.
It has been incrediblyimportant for ALS because I
think most people had not evenheard of the disease before the
Ice Bucket Challenge.
Now everyone knows about thedisease.
(30:23):
It has also brought a lot ofmoney to the foundation and to
other organizations, and one ofmy fellowships when I was
working at Harvard was from theALS Association.
So you know, in a way, theresearch that has also led to
the creation of Q-RALIS is, Ithink, directly supported by
(30:44):
money from the IcebreakerChallenge, Milton
Safenov-Richfield.
So, yes, I think that type ofawareness and that action has
been incredibly important andthat action has been incredibly
important.
Kasper Roet (31:00):
You referenced this , I guess the risk of the exodus
of clinical activity andinnovation away from the FDA
because there are lower barriersand other perhaps lower
(31:20):
barriers and other regulatoryjurisdictions.
That's to say, you didn't evenmention Australia, which has
been one of the major sort ofsiphons of clinical activity
away from the US.
What would you call on thespace to do, like you've been
like, admirably active incalling for and influencing
change?
What would you call on the restof the space to do, like?
(31:41):
What levers might they have topush and pull to join the effort
?
Do you see enough activitygoing on in the greater
landscape.
Matt Pillar (31:51):
Once you start doing these things, you notice
how many other companies aredoing that.
I think the weakness is thatcompanies advocate for
themselves a lot and don't uniteenough to have a united message
.
Because if one company goes andis lobbying for, in this case,
(32:15):
the FDA to look at its ownprocesses, it feels like that
company is just trying to helpthemselves and no one likes that
, because that just feels kindof like it doesn't feel good.
It's like you're trying to skewthe system in your own benefit,
but that's not what we'retrying to do.
There's definitely somethingnot working in the system and
(32:38):
the fixing that will benefiteveryone, and so we've done a
lot of background conversationsalso with companies that maybe
don't want to publicly be partof a consortium, but that we
have the same message so thatthe same message is being heard
over and over and over again.
So because, in the end, if yougive 10 different messages to
(32:59):
someone, they can't remember anyof this.
Right?
I think someone remembers maybethree things very well.
So you want to make sure thatyou have your priorities
straight as a whole biotechsector and then you you give the
same message that, even if itis not part of our consortium,
but an independent message, andso that is something that we've
(33:20):
been doing also with theconsortium, and talked to all of
the large pharma companies thatare active in the ALS space,
and we're all aligned, so it'simportant that we work in that
manner.
Ben Comer (33:32):
Basically, yeah, maybe we can turn it back to
Kira Alice's development andclinical assets right now.
Could you give us a sense ofwhere you are and maybe what
your next big milestones orgoals are with your clinical
programs?
Matt Pillar (33:53):
Yes, I'd be very happy to and just maybe want to
also explain where your clinicalprograms come from.
So the first big discovery thatwas made using patient stem
cells, which were then generatedinto neurons, was that there's
a loss of a potassium channelcalled KD7.2.
(34:15):
The loss of that potassiumchannel leads to neuronal death
in these stem cell models and soif you activate that potassium
channel you can protect againstthat.
We found out it's misplaced.
It's pre-mRNA includes askeptic exon which turns it into
a protein which is rapidlydegraded again, leading to
(34:38):
neuronal death.
But you can protect againstthat with a KD7 opener.
So that is something that wehave now brought to the clinic
and that program is currently atthe end of its phase one.
We've actually run threestudies, four studies in
parallel a MAD study, a multipleascending dose study to look at
(34:58):
tolerability of courseincredibly important.
We've also run a healthyvolunteer study to look at
biomarkers that predict survivalfor ALS but also for epilepsy,
to look at biomarkers thatpredict efficacy in epilepsy,
because the potassium channelsare very important for epilepsy.
We ran a PK study to look atthe three different formulations
(35:21):
, to see which formulationswould be best for these
different indications, and we'vealso ran a patient study to see
how this compound works inpatients.
Most of that data is reading nowto the end of this quarter, and
so this is an incrediblyimportant quarter for us, and so
we're very excited aboutlooking at the results.
Then we have the second bigdiscovery that was made, again
(35:46):
from my co-founder was the lossof our staph-2 micro tubules,
stabilizing protein essentialfor the innervation of your
muscle, so your motor neuronsprotect from your spinal cord
all the way to your muscles, forinstance in your hands and in
your feet.
That innervation is lost whenthere's a loss of staph in tube.
What Kevin discovered is thatit's driven by a mis-splicing
(36:08):
event, and when we realized thatit was just after SpingRoss.
It was approved for spinalmuscular atrophy, a splice
correction ASO targeting motorneurons in the spinal cords of
estimated patients, showingremarkable effects in those
patients.
Really transforming therapythat is marketed by BioChip has
helped so many differentpatients.
We thought we can do that alsofor restoring staph in two
(36:35):
levels and bringing staph in twolevels back to normal, which
again is lost in almost everyALS patient.
At this moment we're running adose range finding trial in six
different countries wherepatients are dose-free for D-glu
that have injections into theirspinal cord with an ASO, an
incisor oligonucleotide thatrestores these staph name levels
, and we are now basicallyexpanding on two different dose
(36:57):
levels to see which of thesedose levels is going to be
effective for following patientsfor an extended period of time.
We're looking at biomarkersthat predict efficacy,
neurofilament and compact muscleaction potential, which
measures this innervation, andwe're going to read that out in
the first half of next year.
Ben Comer (37:17):
And what phase are you in on your clinical trials
with those two?
Matt Pillar (37:20):
So I would say that it's now in a phase two phase,
but with these programs you kindof adapt from phase one to
phase two.
With the KV7, we're at the endof phase one and we're planning
to start phase two trials at theend of the year.
Ben Comer (37:38):
With the KV7 opener, which prevents the potassium
channel from shutting down,which then prevents the neuronal
death?
Does that have to beadministered very early on after
diagnosis of ALS, or when doyou have to catch the patient to
?
Matt Pillar (37:54):
prevent that from closing.
Ben Comer (37:55):
Yeah, that's a great question.
Kasper Roet (37:57):
So ALS is a progressive neurodegenerative
disease.
Matt Pillar (38:00):
So ALS is a progressive neurodegenerative
disease and so other than, forinstance, parkinson's, where if
you have symptoms you've lostalmost all of your dopaminergic
neurons, so there's not a lot toactually protect it.
Still, in ALS, when people havedeveloped symptoms, they still
have a lot of their motorneurons and so over time there's
motor neurons that are stillhealthy, there's motor neurons
(38:22):
that are sick and there's motorneurons that have died, and so
obviously at the end of thedisease a lot of neurons have
died, but at the beginning not.
So in essence you can treatanywhere and have an impact on
the disease.
But in reality the earlier youtreat, the bigger impact you
will have on preventing loss offunction.
So the earlier you treat, thebigger impact you will have on
preventing loss of function.
(38:43):
So the earlier you treat, thebetter you are at picking up
effects of a potentialtherapeutic.
And so early treatment I think,has become kind of a norm for
all neurodegenerative diseases,not because the therapies don't
work if you treat later, butjust because that's where you
have the biggest impact on thedisease.
Kasper Roet (39:03):
We're going to run short on time here, so just a
few more questions and thenwe'll chat.
I talked too much, no, no, no,you're doing great, terrific
responses.
It's been a super meaningfulconversation.
I like the global aspect of it,but in keeping with progress at
Curalis, you mentioned that youwere one of the fortunate
companies to have a presentationat JPMorgan.
There are so many biotechs herewho don't have opportunities to
(39:25):
present at the conference.
They're here for the ancillaryactivity.
How did that go?
Matt Pillar (39:33):
It was a great honor to be invited as a private
company to present at theJPMorgan conference.
I thought it was a greatsuccess.
Kasper Roet (39:44):
I didn't anticipate that you would tell me oh, it
was awful man, I mean it, justit spiraled yeah.
Matt Pillar (39:50):
Oh, we got some good questions back also because
there have been failures in theAOS space and how do we look at
that?
And yeah, I don't want to go toodeep into it, but the
traditional approach ofcompanies has just been looking
at mechanisms that may play arole in disease and then having
a compound, or usually a smallmolecule, that acts on that
(40:11):
mechanism and then hoping thatit does something.
We're following it really froma genetic approach.
So we actually have.
We're the leading company inthe development of therapeutics
for ALS because we have threeprograms in development on
genetic targets the.
The last one, on 13, ispartnered with eli still
pre-clinical, but it's thisgenetic approach that we know
(40:32):
works, and so I've been tryingto educate that to people and uh
, and so this was a questionthat we got also at the JP
Morgan conference.
Just want to give you a littlebit more information on that at
Baltimore.
Kasper Roet (40:47):
Yeah Well, I was going to ask you and hopefully
this will answer the question,because we spoke like a week or
so ago.
Two weeks ago, we had theopportunity to chit chat with
you about what we're going totalk about today and I remember
you saying specifically like weknow it works, we have the tools
, and you said now we just needto do it.
So hopefully that question isgoing to be answered.
(41:08):
What's going on right now interms of all right we're going
to go from we know it works, nowwe just need to do it?
Matt Pillar (41:13):
Yeah, so the first gene that was discovered for ALS
is SOD1.
And that was discovered in 1993.
It was approved in 2023.
So it took 30 years to getthrough an approval.
At this moment, if weunderstand what is going wrong
(41:34):
in the genetics of a disease, wecan be in the clinic four years
later with a genetic medicine.
The path from a geneticdiscovery to a development
candidate, to an IND, to a POC,is a scalable path with these
genetic medicines, specificallyfor RNA therapeutics, and so
that is very powerful, becausegenetics makes us understand why
(41:57):
someone gets sick not for everydisease, but for a lot of
diseases.
Kasper Roet (42:01):
We understand the genetics.
Matt Pillar (42:03):
We have now the technology to build that into a
medicine relatively quickly in avery reproducible manner, and
so we have now done.
At Curalis.
We've made four developmentcandidates.
We know exactly how long thattakes.
We know exactly how to do theseAD&D enabling studies.
We've done that multiple timesas well, and we now have also
(42:24):
learned how to actually run POCprograms.
That's not just for ALS right,but there's many other diseases
where that can be done.
And again that comes back againon why we need also a
regulatory framework that fitswith that, because I think as a
humanity you heard me say thisin the beginning no one wants to
(42:44):
be sick.
No one wants their friends andfamily members to be sick.
We have an opportunity to makereally meaningful therapeutics
for many different people in avery fast way relatively to the
past and in a very highprobability for the success type
of matter.
But so we need to do it, yeah.
Ben Comer (43:09):
That's Curalis.
Founder and CEO of Casper Root.
I'm Ben Fommer, very nice.
Kasper Roet (43:14):
And I'm Matt Feller .
You did a much better job.
Ben Comer (43:16):
Oh, thank you, and you just listened to the
Business of Biotech from JPM2025.
Listen and subscribe whereveryou listen to podcasts or take
our video cast in at BioprocessOnline and Life Science Leader.
Thanks for listening and seeyou next week.
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