Latest / The BioHub - by Avetix / Episode 177 - Shane Hegarty - CSO & Co-Founder of Axonis Therapeutics

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Episode 177 - Shane Hegarty - CSO & Co-Founder of Axonis Therapeutics · The BioHub - by Avetix

0:06
So welcome back to another episode of the BioHub Today
0:09
we're delighted to welcome on Shane Hegarty, A neuroscientist,
0:12
biotech entrepreneur and a Co founder of Axonis Therapeutics
0:16
who are a a cutting edge company developing novel therapies for
0:20
neurological disorders. Shane's journey spans from
0:23
groundbreaking research at University College Cork in
0:26
Ireland to pioneering neuroscience innovation at
0:29
Boston's Children's Hospital and Harvard Medical School.
0:32
With a deep passion for unlocking the brain's potential,
0:35
he has published numerous research papers, secured
0:38
multiple patterns, and now leads Axonis in its mission to
0:41
transform the treatment of the central nervous system.
0:45
So join us today as we'll discuss Axonis's pipeline and
0:48
the LEAD program, the next major milestones for Axonis over the
0:52
next 12 to 24 months and Co founding Axonis during COVID and
0:57
the challenges that came with that.
0:59
So thanks so much for coming on. How are you?
1:02
All is good now, thanks a million for reaching out to
1:05
invite me on the podcast. I've listened to a number of
1:08
episodes and there's a great, you know, caliber of speakers
1:11
have begun before me. So it's an honour to be joining
1:15
the, the, the the show, let's say, and great to reconnect with
1:19
yourself, Tom, after, you know, we've had a lot of previous say
1:23
catch up. So feel hopefully feel very
1:25
natural because of that. Then happy to speak about exams,
1:28
the story and tell you a little bit more about myself and also
1:31
the plans we have in the future as a company.
1:34
Yeah, for sure. But look, excited to have you
1:36
on. And let's just start off with a
1:37
little bit about your journey through the field and how you
1:40
how you got to where you are today.
1:41
So you've spent more than 15 years working on the biology of
1:45
the nervous system and the mechanisms behind new protection
1:48
and regeneration. And take us through your journey
1:51
through the field. How you got to where you are
1:52
today? What what sparked your interest
1:55
in neuroscience and how did your academic work ultimately lead
1:58
you towards building a a biotech company?
2:01
Yeah, it's, it's, it's a long story.
2:03
I could suppose I can give a couple of highlights now and
2:05
maybe tell you where the, the the story began, you know,
2:09
really back in Cork in Ireland, where I was born.
2:12
And that's where I kind of began to uncover my passion for
2:16
neuroscience. So I had an interest in, you
2:19
know, biology, chemistry, physics, maths as a whole.
2:22
And I, I picked a course that gave a flexibility to study
2:26
these areas. But when I was exposed to
2:29
neuroscience for the first time in that undergraduate, you know,
2:32
it was very obvious to me that this was an exciting area.
2:35
And also an interest in psychotherapy based based on my
2:39
mom's kind of interest in that area too.
2:41
So there are some of those books lying around, kind of heavy
2:43
reading, but really interesting about how how how the mind
2:47
works. And actually when I went
2:49
travelling on a break from college one year, I got this
2:52
book. It was called My Stroke of
2:54
Insights, and it was about a Harvard neuroscientist who had a
2:57
stroke. And for her to explain what
2:59
happened to her, she had a couple of chapters on the brain,
3:02
how it works and how she almost had to retrain her brain to be
3:06
functional again at the end. So I knew from those little bits
3:09
of experiences that neuroscience was the area that I was
3:13
extremely passionate about. I just had this almost
3:17
insatiable interest in how the brain works, you know, what goes
3:21
wrong in dysfunction, the potential of the human mind, and
3:24
just wanted to figure out, you know, how to 1st understand it,
3:28
but also maybe leverage that understanding to help people in
3:32
the future in, in any way, what shape or form.
3:35
So in that course at UCC, there's a bit of a risk when you
3:39
pick it, you don't get exposed to a lot of the subjects.
3:42
But you know, based on that, you know, summer, I said, I'll,
3:45
I'll, I'll go for it. And what I found in the course
3:48
were a lot of teachers who were equally passionate about the
3:51
topic and they were very patient with me.
3:54
They're very understanding of, you know, all the questions I
3:57
had, the curiosity I had. And they just gave me a lot of
4:00
opportunities to dig deeper, even just little stints in labs
4:05
and things like that. And eventually that evolved into
4:08
me pursuing research in these labs and going to get grants
4:13
from the Irish government to support PhDs and post doc
4:17
scholarships and things like that, that were enabling me to
4:20
work on projects that I kind of conceived with the professors.
4:24
So I felt like they were my own and I really would have to dive
4:27
into it and, and kind of drive, you know, a lot of, you know,
4:32
research that we did at UCC that was quite productive in terms of
4:36
the output. And I learned a lot about the
4:38
process of research there. They really trained me how to
4:41
be, you know, you know, a neuroscientist overall.
4:45
And yeah, that's probably how the journey began, really.
4:48
And you know, it evolved from there, of course, over to to
4:52
Boston and other guards and happy to get into that part of
4:55
the journey as well. Nice.
4:57
And before Cofan and Ox, honestly, you were a faculty
5:00
member at University College Cork and then as you mentioned,
5:03
Boston Children's Hospital and Harvard Medical School.
5:06
What were some of the key scientific discoveries or
5:09
insights from from that period that you could that convinced
5:13
you into that this biology could translate into real
5:16
therapeutics? Yeah, I think that, you know,
5:18
there are two key experiences, both the research I did in
5:22
Europe and kind of what I was looking for at Boston Children.
5:25
So I, as you said, I had worked my way up to on to the faculty
5:29
of University College Court and I was, you know, working on this
5:33
area that I was very passionate about nootrophic factors for
5:36
Parkinson's disease. And unfortunately at the time
5:39
there were a lot of failed clinical trials in the area.
5:42
And so why we were able to kind of really characterize is
5:46
exquisitely the bio allergy, the mechanisms, how these
5:49
neurotrophic factor work. I think they were having
5:52
limitations clinically. And we've given it a lot of
5:54
reasons there, but some of it had to do with maybe how, you
5:58
know, things we understand about development might translate to
6:01
an, you know, an adult disease brain.
6:04
And I was getting a little bit worried about that.
6:06
So I kind of wanted another solution to the same problem.
6:10
And that's why it was offered a Boston Children's Hospital in
6:13
Harvard Medical School. When I spoke with Professor Ji
6:16
Gang, he he was working in adult systems of the brain and looking
6:21
to cell autonomously reprogram neurons to be able to survive or
6:26
regenerate in kind of in in kind of degenerative conditions.
6:30
And that was very compelling to me based on what I learned about
6:34
the limitations of what I've been doing before.
6:36
And so it was a big decision to leave a tenure track position in
6:40
a different Irish university in Ireland to decide to join Boston
6:44
Children's instead. But the opportunity to pursue
6:47
cutting edge research in a highly resourced environment in
6:51
Jigang's lab was something I just couldn't turn down.
6:54
And I felt, you know, that was the time to do it.
6:57
And so against probably a lot of the well wishes of my advisors,
7:01
you know, I, I kind of almost demoted myself back to the front
7:03
lines of the research lab. But at, uh, in that lab, in
7:07
Jigang's lab with the team that we had there, we were able to do
7:11
amazing things. We had very large scale in vivo
7:15
phenotypic projects, some utilizing AV CRISPR technology
7:19
to screen thousands of genes for their role in the brain and a
7:22
separate screen working on nor modulatory mechanisms.
7:26
So what was brilliant about the way Jigang thought was set up
7:30
exquisite probably model systems and then do unbiased screening
7:34
and let the data tell you what's the best, you know, approach.
7:37
So quite exploratory, large scale, very intensive
7:41
throughput. And that's how we discovered
7:43
very exciting new things, uh, which we ended up, you know,
7:47
filing IP on and spinning out into Examiner's therapeutics.
7:51
And you know, which eventually ended up with our focus now on
7:55
the 1st in class therapeutics to, for a novel target known as
7:59
KCC 2. So I kind of learned about
8:02
translation, I learned about different types of approaches to
8:06
research. I think in Ireland we are
8:08
resource constrained, resource constrained constraints.
8:11
We have to do a lot of deep thinking before we did anything.
8:14
We couldn't really explore everything, which was important.
8:17
That's an important mind mindset for even running a biotech
8:21
company when you're making decisions on what to focus on,
8:24
what to prioritize on what to achieve in a particular time
8:27
bound manner. Because a lot of the post op
8:30
scholarships that I had, lot of the grants I had were time bound
8:33
and I really had to deliver in a narrow period of time to to pro
8:39
to progress. So that was great training in
8:41
Ireland from that perspective. But in Boston Children's
8:44
Hospital and Harvard Medical School, I opened my mind kind of
8:47
to broader possibilities. It wasn't, it was less about
8:51
maybe incremental understanding and progress and it was more
8:54
about redefining whole therapeutic areas or
8:58
understanding the brain at a much deeper level about complete
9:02
novel approaches. So that was having those two
9:05
experiences were essential and I know which one to lean into in a
9:09
given, you know, for a given challenge.
9:12
So I think that's it was very unique training.
9:14
It wasn't, you know, it wasn't following a book to have those
9:18
different experiences, but I think they added up to who I am
9:22
today and particularly when I was ready to make that
9:25
transition from academia into the biotech sector.
9:30
Amazing. And just talk us through like
9:32
when you and your Co founders came together to launch Axonis
9:35
Therapeutics, what problems were you really trying to solve?
9:39
Like was there a particular unmet medical need in
9:42
neurological diseases that you felt the field wasn't addressing
9:45
effectively? Like was there particular gaps
9:47
in neuroscience which you you thought you could maybe come in
9:50
and build a company around? Just just talk us through that
9:52
moment when you were going to when you were looking to launch
9:55
a new Co? Absolutely.
9:57
I think you know, when we when we launched exams, we actually
10:00
had a couple of programs and company was built around
10:03
discoveries made in Boston Children's Hospital, Harvard
10:06
Medical School in G Gang's lab and you know that lab works on
10:10
translational neuroscience. It tries to model things so we
10:16
can discover new solutions to problems that we haven't
10:19
addressed yet. So I, you know, the
10:22
neuromodulatory screen where we found that only the KCC 2
10:26
mechanism could restore inhibition to the spinal cord
10:31
for functional benefit. That was all based on, you know,
10:35
clinical data using neuromodulatory devices.
10:38
So if we can use these epidural stimulation devices to restore
10:42
activity to the human spinal cord, how is that working?
10:45
Why is that happening? But why is that tissue having,
10:50
uh, EI imbalance problems? Umm, So we dug into the
10:53
molecular mechanisms of that and that's what led led us
10:56
unbiasedly to finding KCC 2 as a way to restore balance to the
11:03
CNS. While all the other mechanisms
11:05
that we tried, mainly things that are standard of care were
11:09
failing. So that that was how we were so
11:12
committed to KCC 2 because that level of functional benefit we
11:17
were able to achieve in the preclinical studies was beyond
11:21
what was ever shown before. So we knew we were on, on to
11:23
very fundamental biology, a very novel interventional approach
11:28
where, uh, we're fixing the brakes of the nervous system,
11:32
let's say. Uh, so that was very exciting.
11:35
And it was initially our goal was to translate this spinal
11:38
cord injury research that we had found, uh, back in the lab.
11:41
But over time, as we learned more about the target and its
11:45
biology and its importance in epilepsy and pain and even its
11:49
genetic validation for epilepsy, we began to evolve the company
11:55
to focus on making a number of KCC 2 therapeutics and to work
11:59
on these indications where the the human biology aspect is a
12:04
little bit more the rest, like I've said for epilepsy and pain.
12:07
So I think why did we want to, you know, spin out the
12:11
technologies? I think it's because the
12:13
exciting phenotypes have been proven in the academic space.
12:17
And while we could have dug a little bit deeper and, and
12:20
others did later on, I was more compelled to figure out, now
12:24
that we have this benefit, can we translate it to improve the,
12:28
you know, the lives of patients? Let's that's where in my mind we
12:31
find out yes or no, whether this is actually helping anybody.
12:35
So to be able to directly translate these discoveries into
12:39
new medicines was the quickest way to make an impact and, and
12:44
patients and also to translate our discoveries most
12:47
meaningfully. So that that became a driver for
12:50
me personally. And because we were lucky enough
12:53
to find ourselves in Boston, it was obvious there was a biotech
12:57
ecosystem there that wasn't necessarily in other places I'd
13:01
been before that, you know, gave opened the door for that
13:04
opportunity. For for people that might not be
13:07
as familiar with Acts Honest Therapeutics, could you just
13:09
give us like a sort of high level overview of, of what the
13:12
company does as well as the broader mission you and the team
13:15
are pursuing within neurological diseases?
13:18
Just give us a yeah, sort of full breakdown of the company.
13:22
Certainly. So umm you know as I said the
13:25
company's evolved over the years, but now we're fully
13:28
focused on a single therapeutic target, KCC 2.
13:32
So we are developing first in class oral small molecule
13:36
therapeutics for that target and it's the potassium chloride Co
13:40
transporter 2 and it plays an essential role in enabling and
13:46
maintaining inhibition in the brain throughout the lifespan.
13:51
So we are aiming to restore functional inhibition in CNS
13:56
disorders where there's an imbalance in in activity, so
14:00
hyper excitability issues or disinhibition of circuits.
14:03
And that is a fundamental problem that shows up across
14:06
many different CNS disorders. It might show up in different
14:10
parts of the CNS leading to slightly different issues, but
14:13
fundamentally there's a circuit that's disinhibited and that if
14:17
you restored inhibition, you would alleviate the issue and
14:21
restore balance and normal function to that brain circuit.
14:26
So for us, this means that we want to treat epilepsy, pain and
14:31
other CNS disorders that have excitation inhibition imbalance
14:36
leading to the pathology. And what's unique about our
14:40
mechanism is it's a homeostatic mechanism.
14:45
So we really are restoring balance to circuits.
14:49
We're not, you know, increasing inhibition so far that it can
14:53
also lead to side effects where you might have, you know, a bit
14:57
of sedation or some of these side effects that are commonly
15:00
seen whether existing standard of care nor modulatory drugs.
15:05
Because we're going after this normalisation mechanism, we hope
15:10
to restore benefit without having to have a burden of side
15:15
effects that have become accepted and also limit the use
15:19
of these medicines we have. And there's something unique
15:22
about KCC 2 that no other target can do.
15:26
It sets up the ability of the brain to respond to inhibition.
15:30
So sometimes in diseases or disorders you find that GABA
15:36
can't work properly anymore. And adding a GABA based drug
15:40
won't work either because if the the cell can respond to GABA
15:45
then you don't get any inhibition.
15:47
So by potentiating KCC 2, we can make the CNS respond in a very
15:54
physiological normal way to the endogenous GABA.
15:58
And what we see in many disorders is a drug resistance
16:02
emerging and part of that drug resistance may be due to KCC 2
16:06
hyperfunction. So we're aiming to correct the
16:09
balance, restore a functional inhibition without having some
16:14
of the issues and tolerability problems that can emerge when
16:18
you use agents that just globally repress brain activity
16:23
to try to, you know, counteract seizures or, or chronic pain.
16:27
So I think that's where the unique benefit is and it's a
16:31
very precise mechanism targeted for the brain.
16:34
So that's, that's really the, the, umm, reason why we're so
16:39
committed to this single target and the reason why a lot of
16:42
people have become excited about what we're doing here at Xanax
16:45
over the years. Yeah, amazing.
16:47
And you, you mentioned a little bit about KCC 2 then, which is a
16:52
first class oral designed to restore inhibitory signal in the
16:56
nervous system. Can you just talk us through
16:58
like how does this drug work mechanistically?
17:02
What diseases are you initially targeted and like what actually
17:05
makes the drug different to to to maybe what out there or is
17:09
this quite an uncharted field of of medicine that you go in going
17:13
through? Absolutely.
17:15
So we are making first in class oral medicines.
17:18
And because, you know, first in class means no one's really done
17:21
it before. So we do have to kind of almost
17:24
blaze a trail to show what this mechanism can do.
17:30
Fundamentally all we, we at the end of the day, we're going to
17:33
have to demonstrate that it can treat seizures, it can reduce
17:37
chronic pain burden, but the path to getting there might be
17:40
slightly different for what we are doing compared to what
17:43
people have done in the past. So the what's beautiful about
17:47
the mechanism, as I said, or the target is that it's selectively
17:50
expressed in the brain, which makes it a great molecular
17:55
target for a small molecule that goes everywhere in the body.
17:58
So the even though it goes everywhere in the body, it has
18:01
this selective activity on the CNS.
18:03
So we don't have to worry about other tissues or organ systems
18:07
in the body having side effects that are on target.
18:10
That's a great advantage for the target.
18:13
That's DNS specificity. It also acts in neurons only.
18:18
So we're really targeting the cell types that have a problem
18:21
in neurological disorders, typically the especially
18:24
disorders where there's hyper excitability or disinhibition of
18:28
a circuit that's leading to seizures, chronic pain, movement
18:32
disorders, psychiatric problems. So we are acting directly on
18:37
those circuits to correct inhibition.
18:40
And when we're restoring ambitions to the circuits, they
18:42
should function more normally and we can alleviate the
18:46
pathological issues without needing to depress the activity
18:51
or repress the activity of the rest of the CNS.
18:54
And that selectivity for the disinhibited circuits is really
18:59
unique to the KCC 2 potentiation mechanism that we're advancing
19:04
now through clinical trials. Amazing.
19:08
And like I think historically drug development within CNS in
19:12
the central nervous system has been one of the most difficult
19:15
areas in pharma and biotech historically.
19:19
From your perspective as both a neuroscientist and a Co founder
19:23
of a biotech, why do you think CNS drug discovery has been so
19:27
challenging over the years and what advances in biology or
19:31
technology do you think are starting to to try and change
19:34
that? Yeah, I think there's a lot of
19:37
different challenges in drug development for the CNS.
19:41
You know, there's, there's getting your therapeutic to the
19:43
brain at sufficient amounts that it can have its benefit without
19:48
affecting other parts of the body.
19:50
And that that that's just a, you know, a modality problem.
19:54
And we're making more progress than ever on small molecules and
19:57
even other advanced modalities to get over the barrier of the
20:01
blood brain barrier, let's say that.
20:03
Restricts the therapeutic getting where it needs to go.
20:06
But let's assume we can do that and I think now we can and
20:10
that's getting, we're getting better and better at doing that.
20:13
The preclinical tools that we use now to characterize the
20:17
function of the CNS are much more advanced than what they
20:20
were a decade or two ago. So things like optogenetics, we
20:24
can study circuits, we can model things a lot more deeply than
20:29
before. And obviously we have a lot of
20:31
more ability to do human models like driven by IPSCS and things
20:36
like that. So I think we understand the
20:39
ontology of or pathogenesis of different diseases much better
20:44
and they're much closer to what happens clinically.
20:48
But then really where do every where, where does the rubber
20:51
meet the road for any medicine? It's in the clinic.
20:54
And we're getting better at doing clinical trials in
20:57
neurology. So we need to be able to, you
21:00
know, if we learned anything from oncology, we need to be
21:03
able to stratify patients based on the, the problem that they
21:07
actually have. So what is driving their
21:09
pathology? We're getting better at
21:11
elucidating that. Umm and also how do we measure
21:15
the clinical benefit? So before there was a heavy
21:19
reliance on large populations and we're testing symptomatic
21:23
treatments in these populations and we're asked, we're kind of
21:26
looking at subjective endpoints these days.
21:29
We're getting better and better at least in earlier clinical
21:32
trials and using objective measures of, you know, clinical
21:36
benefit that can be, you know, in our case, we'd be interested
21:40
in electrophysiological readouts of CNS activity and whether
21:44
we've corrected that in a given disorder.
21:47
But also there's been advances on fluid biomarkers and imaging
21:51
technologies like in Alzheimer's, where we can look
21:55
at the, you know, the patholo pathological signatures of the
21:59
disease and see if we can correct them in a more objective
22:03
way. And so sometimes these are
22:05
surrogate endpoints or biomarkers.
22:07
But now that we have these tools and we're continually evolving
22:11
those, we will be able to define the patients better.
22:14
That should be in the trial, we should be able to measure the
22:17
clinical benefit more objectively and we have much
22:20
better tools to get the therapeutic to the right place
22:24
in the CNS. So that's why the field is, you
22:27
know, in my mind primed to be very successful in the future.
22:32
And we will see more and more of these precision neuroscience or
22:38
neurological therapies being advanced and and that's how we
22:42
feel and think about our KCC 2 potentiators as well.
22:46
So that's that's why it's very exciting time for CNS in general
22:50
and why we'll see more and more clinical success going forward.
22:54
Yeah, for sure. And I know it's been one of
22:56
those areas over the past couple of years.
22:58
Obviously oncology will always dominate, but CNSINI obesity
23:02
certainly areas that have been of strong interest particularly
23:06
to, to venture capitals and you've seen some pharma
23:10
acquisitions in that space as well.
23:11
So I think it's definitely, yeah, there's, there's, it
23:13
certainly seems like an exciting time to to be in the CNS.
23:16
Space absolutely, absolutely and long, long made this success
23:21
continue, but I think we're only starting to scratch the surface.
23:25
And you know, there's one other thing that I should add and it's
23:28
about when do we intervene. So I think the CNS field has a
23:32
little bit been victim to we try to treat patients when the
23:36
pathology becomes very severe or late stage and sometimes that
23:40
can be too late to improve things particularly in
23:43
neurodegenerative diseases where a lot of degeneration has
23:46
already taken place and it's hard to bring to restore
23:49
function in that context. So if we have better biomarkers
23:54
or ways of identifying patients earlier, we can intervene more
23:58
early and have better clinical benefits or disease modified
24:02
disease modifying ability with that earlier treatment.
24:06
So you know, not necessarily pre emptive medicine, but moving
24:10
closer to that concept. So I think that's another, you
24:13
know, place where we're going to see enormous clinical benefit
24:17
emerge from as we get better at measuring pathology and
24:21
identifying patients sooner and then matching the right
24:25
therapeutic for that disease stage.
24:27
Because over time different problems can emerge.
24:30
You know, things that maybe start out as excitation,
24:34
inhibition, imbalance could potentially progress to
24:36
degeneration or inflammation or they're all happening together.
24:40
So it's very multifactorial what goes on in different disease
24:45
conditions. They might be affecting
24:47
different parts of the CNS, but a lot of the same problems
24:50
occur. So we need to understand that
24:53
and use the right modalities at the right time to have, you
24:57
know, to restore or treat that that issue.
25:01
And I think that's another opportunity around rational
25:05
polypharmacy. So we can take a drug that
25:08
addresses, you know, nor degeneration and one that
25:11
addresses excitability and one that addresses nor inflammation.
25:15
And you could foresee a future where all three of those could
25:18
be used together to overall have the, the, the, all the factors
25:24
that are driving a pathology treated with individual.
25:28
So I think that's where we should go, but we need all these
25:31
tools in the 1st place. So that's what the team is
25:35
working on. But I think we'll have a great
25:37
way of treating patients with these different tools in the
25:41
toolbox as the field mature in the next decade or two.
25:46
And look, you guys, an Axonist had recently raised a
25:49
significant fundraising round to move its programmes forward.
25:52
So congratulations to you and, and the team on that.
25:56
As you look ahead, what are the next major milestones for the
25:58
company over the next 12 to to 24 months that you and the team
26:02
are focused on delivering? Is it, you know, on the, on the
26:05
clinical side, fundraising side, partnership side, like just talk
26:08
us through what you guys are are most excited about coming up.
26:12
Definitely, I think, you know, we were, we were very honoured
26:16
and delighted to be able to bring together such a strong
26:19
syndicate of investors that believed in our vision and that
26:24
we're excited about the quality of the technology and how we're
26:27
planning to use it. So that was a great, you know,
26:30
recognition of everything we have built here at Axonis you
26:34
know, firstly the KCC 2 discovery engine, then bringing
26:38
these first in class KCC 2 potentiator drugs through the
26:42
whole package to be ready for clinical trials.
26:44
So we, that was, you know, an important moment for us and now
26:48
it's enabled us to, to get those answers because really what we
26:52
need to prove in the next year or two is that when we use this
26:56
novel mechanism, we we get the clinical benefit that we expect
27:01
in the patients of interest, as I said, primarily epilepsy and
27:04
pain for the LEAP program. So that's what we're planning to
27:07
show. We've been, you know, we're
27:09
resourced to do it. And another thing that comes
27:12
with our new syndicate is expertise.
27:15
So these are very, you know, knowledgeable people who are
27:18
sitting on our board from these funds and we're drawing on their
27:21
expertise and their networks expertise to be, you know, a
27:26
better team overall. And we're scaling our company to
27:29
be better than ever I would say. And we're doing things, you
27:34
know, we're growing the pipeline as well that we necessarily
27:38
didn't have that as many options before.
27:41
Now we're having additional programs to make a whole
27:45
portfolio of first in class and best in class KSPC 2
27:50
therapeutics which will be matched to particular patients.
27:54
So that's a very exciting reality of where we are now.
27:58
But what I most I'm looking forward to is to running these
28:03
clinical trials. So we've finished the phase one,
28:06
which was the first part of what we hope to achieve from the
28:09
Series A. And we've demonstrated that this
28:12
novel mechanism is safe, well tolerated, and the drug, you
28:16
know, looks great, gets into the brain and it's it's those
28:18
proportional. So that sets us up to do the
28:22
next step, which is to show for the first time how this novel
28:26
mechanism works in the CNS. We're looking at interesting
28:31
electrophysiological readouts to show that ways that are quite
28:35
novel. And obviously, we're planning to
28:38
get into the patients that have KCC 2 hyperfunction and we want
28:42
to correct that disinhibition and demonstrate how that
28:47
provides clinical benefit in these patient populations.
28:50
So that's really the most important thing that we're
28:53
focused on. And from that, of course, we're
28:56
going to open up the door to all sorts of ER opportunities for
29:00
KCC 2 therapeutics by laying the foundations for how you, you
29:05
know, develop these therapeutics, but also
29:08
demonstrating how transformative they may be for treating
29:12
neurological disorders. So that's really the next, you
29:15
know, 12 to 24 months of the plan for the for the company and
29:20
we're better set up than ever to execute on that.
29:23
Amazing sounds, sounds super exciting and acts honest.
29:28
So the company was founded and and built during the COVID
29:31
period, which was which was challenging for any business
29:35
and, and must have made what you what you guys were trying to
29:37
build even more complicated. What was some of the biggest
29:41
challenges of launching and and growing during that time?
29:44
I would imagine for what you guys are trying to do this,
29:46
there obviously needs to be an element of in person as well,
29:50
never mind the uncertainty of what was going to happen during
29:52
the COVID pandemic as well. But yeah, just talk us through
29:55
what's the biggest challenges were of launching and growing
29:58
the company during that time? Yeah, I think, you know, Axonis
30:02
doesn't have the most traditional founding story.
30:05
And it's very important to to share that the company was
30:09
originally founded by a patient advocate known as Bob Yant, who
30:13
has a spinal cord injury and who's very entrepreneurial, very
30:17
proactive in trying to, you know, push forward new
30:22
treatments and potentially cures for spinal cord injury.
30:25
So it was his vision to address that problem and he was working
30:29
closely with Corey Goodman, who's the chairman of our board
30:34
and another Co founder to to, you know, find ways of doing
30:38
that. And they were working and
30:40
primarily with Ji Gang, he or professor, because they could
30:43
see that he was doing, you know, very exciting breakthrough
30:47
research in this area. So that's kind of the
30:50
ontogenesis of Axonis And as you said, the operations of the
30:54
company, you know, started around COVID, and I think COVID
30:59
almost provided the space for examers, the launch, if you know
31:03
what I mean, because we were very busy in the lab, in the
31:07
research side. We were working on these new
31:09
breakthroughs, very excited, screening thousands of genes, as
31:13
I said. So in a way, it forced us to
31:15
take a bit of a breather and think about what we already had
31:18
and what we should do with it. Should we file IP, which we did
31:22
and made space to think about this company.
31:24
And it was Joanna and Corey who had the vision to, you know,
31:30
it's time to translate KCC 2. And then when the time was
31:34
right, and then I'll have to say a whole separate story on
31:37
getting a visa, it was time for me to, you know, officially be
31:41
part of the team as well. So we that was really the COVID
31:45
wasn't really a barrier. If anything, it made an up, it
31:48
made space in our busy research schedule.
31:52
This, this translation, this opportunity and with Corey and
31:56
Bob supporting that and machine gun, of course, that was the
32:00
what, what helped us launch. And as soon as Joanna started to
32:04
share the story, what we wanted to do with the world, you know,
32:08
we've got additional, you know, E investor, dental investors,
32:11
VCs to be excited about the vision and we kind of never look
32:15
back from there. And we were very blessed as well
32:18
over that period to get a lot of grams from NIH and DoD to
32:23
disdain us as we worked out all these novel things that we were
32:26
trying to do to get us to the point of, you know, raising the
32:30
$115 million series AI was get to the point where we read that
32:36
took many years of that earlier support and, and, and hard work.
32:40
I think, you know, I, I never think as COVID as an impediment.
32:44
I think, you know, beyond our own story, I think it provided
32:47
accessibility to the biotech community.
32:50
A lot of programs became virtual.
32:53
You know, I, I got the luxury of being based in Boston.
32:56
I could go to Harvard eye labs and be part of their training
32:59
programs and innovation challenges.
33:02
But these things began to open up, become virtual.
33:06
And I think that's, you know, that's the greatest benefit I
33:10
think that it could offer ability to bring people in from
33:14
all over the world to be part of this ecosystem strong in Boston.
33:18
And we leveraged that completely and it made made us very
33:22
effective, resourceful and productive in those years.
33:28
Yeah, amazing. And just to finish off, and this
33:31
is a question that we would always ask people that that come
33:34
on the podcast. But if you were to sit down,
33:37
invite any three people for for a dinner, past or present, it
33:41
can be anyone. It can be for biotech, it can be
33:44
for leadership business from sports, from history, like
33:48
whoever you want. If you were to invite three
33:49
people for dinner, who would they be and why?
33:53
Yeah, Tom, you probably won't be surprised by by my first answer,
33:56
but it would be Sir Alex Ferguson person he has to be
33:59
there. And for anyone who isn't, you
34:02
know, a soccer fanatic like myself, he's, you know, in my
34:05
mind the greatest team manager, team builder of all time.
34:10
And he's an all nurturer of talent.
34:13
So he was able to bring very young talented people and, and,
34:18
and grow them up to be, to be stars and, and see that talent
34:21
and integrate them in to teams. So I think that's, that's, you
34:25
know, a skill set than that very people have demonstrated at that
34:29
level. And to have him there and to
34:31
pick his brains, because that's how I think you should build
34:34
teams in any context, even in biotech and to, you know, drive
34:38
that excellence and have those high standards and, you know,
34:41
develop talent. I'd love to have him speak to
34:44
that in a in a dinner. And the next one, you know,
34:48
might be surprising, but it'd be Viktor Frankel, who, you know,
34:51
he came up with this concept of logo therapy.
34:54
He wrote this book that kind of in a way changed my life called
34:57
Man's Search for Meaning. And I think it could be just the
35:00
humans search for meaning. It could be an appropriate title
35:03
as well. And he just speaks about how,
35:06
you know, what drives meaning for people.
35:08
And I think if you want to do anything difficult, hard, that
35:13
requires big teams, that requires a lot of buying needs
35:16
the world to support, you need to create that meaning.
35:20
You need to explain to people why this journey is worth it,
35:23
why they should make so many sacrifices to push this.
35:27
Because what we're doing is very hard.
35:28
And particularly for us, we're first in class therapeutic.
35:30
We're doing many things for the first time.
35:32
We have to convince people of things that haven't existed
35:35
before. And, you know, I think his, his
35:38
thinking about how meaning drives everybody, you know, can
35:42
apply to any scenario. You need to, you need to kind of
35:45
leverage that you need to hook into that in the different
35:48
stakeholders. You need to make this vision a
35:50
reality. So to have him there, you know,
35:52
for that reason would be great. And then, you know, to to
35:55
finalise, I suppose, you know, there's a father of
35:59
neuroscience. His name is Santiago Ramani
36:03
Kiyal, and he was the one to really start to do the very
36:07
early work to study the brain or neurons and everything like
36:12
that. So while he didn't get the
36:13
chance to look at the technologies we have today or
36:17
benefit from that understanding, I think if you could bring him
36:20
in and, you know, ask him what do you think about what we're
36:23
able to do today and what we should do in the future?
36:26
I think he'd have, you know, incredible thoughtful things to
36:31
inform most or teach us how to continue to make advances in
36:34
neuroscience. And of course, with the ultimate
36:36
goal of improving the lives of people with neurological
36:39
disorders. So I think it'd be a fun dinner,
36:42
probably be quite heavy, you know, heavy discussions.
36:45
But maybe, you know, if I brought along a couple of Irish
36:48
guinnesses or something, everyone could be a little bit
36:50
more chilled and open up and collaborate on, you know, some,
36:54
some, you know, meaningful, you know, synergies between them to
37:01
at least educate me to be even somewhat at their level.
37:06
Amazing. Well look, 3 great answers there
37:08
and thanks again. Thanks again for coming on and
37:10
helping us out with this. It was a pleasure to to hear not
37:13
only your story, but but acts on it's journey and how you got,
37:16
how you guys got to where you are today.
37:18
As well as I guess your thoughts on on the CNS space as well,
37:21
which for sure is, is ever growing and I'm sure is, is
37:24
going to be a really hot topic over the next sort of few years.
37:29
So look Shane, it was a pleasure.
37:30
Thanks again for coming on. Great to catch up.
37:33
Absolute pleasure and hopefully I can come back in a year or two
37:36
and, you know, share with you our progress and, and with with
37:41
the evidence we, we need to realise our vision and, and even
37:45
open up further opportunities for the company and this new
37:49
medical approach.