Latest / The BioHub - by Avetix / Episode 89 - Rita Balice-Gordon - Muna Therapeutics

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Episode 89 - Rita Balice-Gordon - Muna Therapeutics · The BioHub - by Avetix

0:04
Welcome back to another episode of the Biohub podcast.
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Today, I'm be thrilled to be joined by Rita Ballas Gordon.
0:11
Rita brings over 30 years of experience in neuroscience
0:14
research, drug discovery, and developments from senior
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leadership roles in biopharma and a distinguished academic
0:21
research career. Prior to joining Mina, she LED
0:24
small molecule biologics and gene therapy programs in
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neurodegenerative and rare genetic diseases at Santa Fe
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Psychiatry and pain programs at Pfizer, and was a professor of
0:33
neuroscience at the University of Pennsylvania School of
0:36
Medicine. Rita, welcome to the podcast.
0:38
Thank you for coming on. Thank you for having me, George.
0:41
It's a pleasure to be here. Brilliant.
0:44
Yeah. Look, really excited for this,
0:45
Rita. And to kick start, can you just
0:48
sort of go back to the beginning and share a little bit about
0:51
your career journey and then what ultimately drew you into
0:54
biotech leadership? Me too.
0:57
So I have wanted to be a scientist since I was a little
1:01
kid cooking in the kitchen with my mom.
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And I was the pesky child to always ask, you know, why are
1:06
you doing this? Why are you adding baking
1:09
powder? What happens, you know, when you
1:11
add the salt and how, how come you, you know, add the yeast
1:14
before you add the salt? Questions like that, I'm sure I
1:17
drove her absolutely Batty. And back in those days before
1:21
the Internet, she would send me to our trusty resource, which
1:25
was the Encyclopedia Britannica in the living room to look it
1:29
up. And I became aware of two things
1:32
then. So first of all, how important
1:34
it was to ask questions and keep on asking till you got an answer
1:37
that you understood. And my mom has many wonderful
1:40
qualities, and among them is the ability to explain things in a
1:43
very clear way that kind of leads you to the next question.
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And that's something that one of many lessons I learned from her,
1:50
I guess, over my almost 65 years.
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And then that kind of led to a real interest in science in
1:59
school and then pursuing science in my undergraduate days at
2:04
Northwestern University, which was so early in the field of
2:08
neuroscience that there were only one or two courses offered
2:12
at that time, which I took. And was inspired by a professor
2:17
by the name of Rea Rutenberg, who was working on a part of the
2:22
brain called the hit the campus where he was studying learning
2:25
and memory. Perhaps the two most fascinating
2:28
behaviors that we as humans show that of course are mediated by
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this essential circuitry in our brains.
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And I worked with him for a couple of years, really my first
2:40
lab experience learning how to ask questions about the brain,
2:45
how to answer them, sort of developing A toolkit to not only
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ask the questions, but but begin to find some answers.
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And that led me to a graduate career, which led me to a post
2:57
doc. I did a post doc at the advent
3:00
of in vivo imaging to understand how synaptic connections in the
3:06
brain are plastic and are shaped by experience, and then how that
3:10
plasticity and experience changes the output, which is
3:14
behavior, which of course changes experience in
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plasticity, and how to really study this loop connecting brain
3:21
circuitry to behavioral outputs. And that's what I did for my
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academic career. I was you, as you mentioned in
3:27
the intro, a professor of neuroscience for many years at
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the University of Pennsylvania School of Medicine.
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My lab and I studied the role of neural activity and shaping
3:37
synaptic connectivity, and I used imaging and
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electrophysiology and molecular and cell biology tools in my
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toolkit to answer those questions.
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And about the time I got tenure, which would have been maybe
3:51
middle 2000s, like 2005, 2006, something in that time frame, I
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was given a brand shiny new lab, beautiful new lab space in a new
4:00
building. And I moved in and we had a
4:03
massive leak about two weeks later.
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So my lab was moved to to temporary new quarters on a
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neurology floor. And I had the incredible good
4:12
fortune of having my office and lab be adjacent to that of a
4:17
clinical neurologist by the name of Joseph Delmal, who was
4:21
studying what at that time were the first patients with a very
4:25
mysterious syndrome that manifest as acute onset deficits
4:32
in learning and memory. And it turned out there's
4:36
patients through the work of of Joseph and his colleagues in
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those early days had an autoimmune process going on in
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the brain that was mediated. We came to discover in working
4:49
together auto antibodies against different synaptic components.
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And this collaboration that was completely serendipitous and
4:57
fostered by, you know, location, location, location being in
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proximity to one another as scientific discussions were were
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happening are really led to an almost 15 year collaboration and
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a really productive period of time understanding the
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pathophysiology of these diseases.
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And it was the first time in my career that I moved from basic
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science to asking questions about human functional
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neuroscience and was the first time in my career I started to
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ask myself, well, what can we do about it?
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How can we develop better treatments for patients to
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deplete these auto antibodies against synaptic proteins and
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improve their cognition and other behaviors much more
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rapidly than the innovations in the toolkit at the time would
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support? So they were interventions like
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IVIG and plasmapheresis, which were effective in some patients,
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but not terribly effective at depleting auto antibody titers
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in the CSF in the brain itself. So I wrote what I thought was
6:00
the best grant of my career to develop an idea for a potential
6:06
treatment and it was one of the very few grants in my career
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which was not funded and the reason was ridiculous.
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It was the science was good, the idea was great, the reviewers
6:16
like the work we propose. But the criticism was this
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person has no credentials to do drug discovery and early
6:23
clinical development. So I decided to fix that by
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doing a sabbatical advisor. This was like the 20/10/2011
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time frame I just hired to build a neuro immunology group.
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By that point, my lab had become quite well known for working on
6:40
the cell cell signaling between glia, cell type in the brain and
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neurons, and I went to Pfizer on sabbatical to build this group.
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And the next thing you know, I never left.
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I had intended to return, but I enjoyed the applied nature of
7:00
doing science in a biopharma setting, the highway team
7:06
centric and collaborative nature of the work and the fact that
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you could do almost anything very rapidly if the idea was a
7:13
good one. And you can elicit, you know,
7:15
senior management support for it.
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And then before I knew it, I became one of their senior
7:19
leaders and I ended up leading the psychiatry portfolio and
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then the pain portfolio, which was based in the UK.
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And when Pfizer decided to shift its focus away from
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neuroscience, I became the global head of rare neurologic
7:34
diseases at Santa Fe. And as you noted in the intro, I
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ended up leading on the rare side, mostly lysosomal storage
7:42
disorder therapeutic concepts from early discovery to early
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clinical work on metabolic disorders and gene therapies.
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And on the neuro side, the work was focused mostly on
7:54
understanding mechanisms of multiple sclerosis, in
7:58
particular how to enhance repair in the brain and relaxing and
8:05
progressive forms of disease. We worked a lot of Parkinson's
8:08
disease, mostly disease modifying therapeutic concepts
8:12
and ALS. And I did that for a number of
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years and enjoyed the leadership role and my colleagues very
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much. We brought a number of novel
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concepts across rare and neuro to Phase 1 and beyond and did a
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couple of very impactful collaborations.
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One of which ended up in a drug that is now being registered for
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the treatment of relapsing Ms. and secondary progressive Ms.
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And a second collaboration with a big neurobiotech company
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called Denali on a novel inhibitor that had significant
8:48
potential for neuroprotection. And it is still in in clinical
8:52
development. And I realized that I had a
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number of ideas that I couldn't pursue in the context of a big
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pharma company. And I wanted to try my hand at
9:03
biotech. And I was asked to buy AVC Novo
9:08
Holdings based in Copenhagen, to review a foundational piece of
9:12
science from a Danish scientist that they were thinking about
9:17
building a neuro company around. And Santa Fe, as you may recall,
9:23
is a multinational pharma company with headquarters in
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Paris. I was in Paris and took a trip
9:28
over to Copenhagen to meet with them and gave them my honest
9:31
opinion. And then they asked me how I
9:33
would build a company around that foundational piece of
9:36
science that I gave them my two cents.
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And the next thing I knew, I was MUNA and leading the company as
9:43
ACEO after a successful raise with my partner in crime, Anders
9:48
Hinsby, who's based in Copenhagen.
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It was brought in by Novo very early to to work with me and
9:55
lead the company to greatness. And I'm very happy to say that
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after joining MUNA in 2020, first is the Chief Scientific
10:03
Officer and then as the CEO as we closed our Series A round,
10:08
which was the largest round in 2021 for a European company.
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We've brought our first program just today to phase one.
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We are in the clinic in healthy subjects testing the safety and
10:21
tolerability of a what we think is a best in class small
10:26
molecule TREM 2 agonist for the treatment of Alzheimer's
10:29
disease, a wholly homegrown program from chemistry through
10:34
biology to biomarkers to clinical trial design.
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And we're super excited along the way.
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We built out a portfolio of other therapeutic concepts for
10:44
other neurodegenerative diseases and we built a platform that we
10:49
call My Map, which is unique among biotechs and uses spatial
10:55
transcriptomics to understand how individual cells in the
10:59
brain respond to misfolded protein pathology.
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So we started with human samples from Alzheimer's disease
11:07
patients, post mortem samples and applied a series of
11:11
techniques developed by one of our scientific Co founders, Bart
11:15
Just Trooper and applied to the study of mouse models of
11:19
Alzheimer's disease. We at MUNA applied these to
11:22
human samples for the first time and built out a platform that
11:26
was the subject of a big partnership with GSK at the end
11:31
of 2024 and which continues to this day.
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To understand what it is that makes some cells resilient to
11:40
the effects of misfolded protein pathology in some patients and
11:43
how those cells differ from cells that succumb to the
11:47
effects of protein pathology. And hopefully understand
11:50
something about where the next generation of disease modifying
11:54
therapeutics will come from. So life is good.
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I'm really proud of what we've built at MUNA and I'm excited
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for what the future holds. Yeah, yeah.
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So that's my career in a very big nutshell.
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Yeah, I didn't know, but yeah, you've got, you've got that
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combination now I guess of academic research, large farmer
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and now leading a small biotech as as well in terms of the
12:17
transition into into muna, coming from large farmer into a
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small biotech, how how have you found that?
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How's the dynamic been for you? Now I got asked this question
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quite often, as you might imagine, about the transition
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from academia and applying that skill set to big pharma and then
12:35
big pharma to biotech. And I have to say that being an
12:38
academic is very entrepreneurial and I don't think a lot of
12:42
people necessarily think about it that way.
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But you're really developing the idea for the product.
12:48
You are raising money to develop the product, You're advertising
12:53
the product. And that here, I mean,
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publishing papers and giving talks and, you know, recruiting
12:57
people to to staff your lab to work on the product.
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Their parallels with biotech are are are many.
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And in big pharma, the skill set I ended up using the most often
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was the skill set that you developed as an academic sitting
13:13
on study sections for grant funding agencies where you've
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got lots of good ideas. There are lots of resources to
13:22
fund those ideas, but you can't do everything and you have to
13:25
make some very hard choices along the way about what work
13:28
meets the bar for funding and what work needs a little bit
13:31
more time to mature before it would be ready to for for prime
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time, as it were. And that is the skill set that I
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used when I was in a big pharma setting.
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And frankly, that's the skill set I use in biotech all the
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time. You can do anything, but you
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can't do everything. It's all about the trade-offs
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and I think understanding the basic science arena and what Big
13:53
Pharma is looking for has helped my colleagues in me develop more
13:58
effective strategies to position MUNA well to compete and what is
14:02
a tough market, you know, for every therapeutic area these
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days. Yeah, absolutely.
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I think touching on that as well, especially with the
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neurology and neurodegenerative, there's been a lot of sort of
14:12
biotechs in that markets at the moment is a very condensed
14:17
condensed position within the farmer world.
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How does how does your approach that mean to differentiate to
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perhaps others out there targeting like neurodegenerative
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diseases? Well, I think fortunately Muna
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entered the fray of the field as a neurodegeneration focused
14:34
biotech at a point where focusing on human biology had
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gotten a lot of traction. And what Muna's secret sauce was
14:43
in 2020 and 2021 as we are getting started is taking what
14:47
we called as much in human as its practical approach to early
14:52
stage drug discovery and drug development.
14:54
So we developed, as I mentioned, a platform that based our
14:59
insights about potential targets from an analysis of human tissue
15:03
from healthy controls in patients including individuals
15:07
who had Alzheimer's pathology but no evidence of cognitive
15:11
impairment and were hypothetically resilient.
15:14
And then to ask that question, we also analyzed the brains of
15:19
individuals who died past the age of 100, so on centenarians
15:25
with and without cognitive impairment and all of whom had
15:28
pathology. So truly resilient if you were
15:32
104 and had Alzheimer's pathology, but no evidence of
15:36
cognitive impairment. And that was sort of the
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foundational all in human approach We then took, we built
15:43
a bioinformatics platform and a toolkit to analyze what was
15:47
really a massive data set and then mined that data set for
15:51
potential targets. We built human cells centric
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assays. So human induced pluripotential
15:58
cell neurons and microglia and other cells to test our
16:03
biologies in. We used humanized models in
16:06
animals wherever feasible, and then we got to the clinic as
16:11
soon as we possibly could. Because ultimately, no matter
16:14
how good the preclinical data looks and how great a story you
16:18
can tell, the proof really lies in safety and tolerability first
16:23
and foremost in patients. And then of course, efficacy in
16:27
patients who are struggling with one or more symptoms of disease.
16:30
And this all in human approach, spending as little time as we
16:35
could in preclinical models that we know don't translate, but
16:39
from which you can learn something important about
16:42
mechanistic biomarkers, about pharmacology and
16:45
pharmacokinetics, the way your compound behaves in an in vivo
16:49
setting. I'm not saying animal models are
16:52
unimportant. I'm just saying that we stopped
16:55
being seduced by the efficacy we saw in those animal models and
16:59
we really focused on a human biology approach and this is
17:03
stood as in good stead not only for our TRIM 2 program, but for
17:06
the other programs in our portfolio.
17:08
Yeah, fantastic. And going back to the point you
17:11
started off, obviously you mentioned there based over in
17:13
Copenhagen, you yourself obviously are based in the USI
17:17
know when we've spoken before, you mentioned your, your team is
17:19
spread across the globe. Yeah, how, how, how, how does
17:23
that work for you? How do you keep everyone aligned
17:24
being CEO, running a biotech with everyone in different
17:28
countries? How do you keep everyone aligned
17:30
and at most places to get the job done?
17:33
I think we're fortunate to be living in an era where science
17:36
is very much a global enterprise and has been for quite some
17:40
time. So it felt pretty natural to go
17:42
where the talent resided. And of course, in Copenhagen,
17:48
very fortunate to have a very entrepreneurial ecosystem and a
17:52
lot of great science talent, including many colleagues with
17:55
former biopharma experience from the great neuro and other
18:00
biopharma that are based in Denmark and in the Nordics.
18:04
And then across the rest of Europe.
18:06
We have a platform group that's based in living just outside of
18:09
Brussels. This is a group where we were
18:13
fortunate to be able to recruit the foundational colleagues for
18:17
the platform from the lab of our scientific Co founder, Bertis
18:21
Trooper and really get our platform off to a running start
18:25
very quickly. And there is a extraordinary
18:28
concentration of talent both in neuroscience in
18:31
neurodegenerative diseases, Alzheimer's, other disorders as
18:35
well as spatial transcriptomics at that group.
18:37
So building a group there made a lot of sense.
18:40
And then in the US, of course, of biotech hubs on the East
18:43
Coast, on the West Coast made it pretty straightforward to find
18:46
the talent. And then we knit it together
18:48
with a good electronic tools like the one we use it today to
18:51
record the podcast. Lots of air miles, lots of early
18:57
days and some late nights for our colleagues in Europe and
19:00
Goodwill. That makes the entire enterprise
19:03
work. I'm fortunate to be working with
19:06
a team of incredibly passionate and dedicated colleagues.
19:11
As you know, any kind of drug discovery and development effort
19:15
requires really a broad array of skill sets, and I'm happy that
19:20
we've gathered them under the moon a banner, and it's really a
19:25
privilege to work with such talented, committed people.
19:29
Yeah. And I know before as well, you,
19:31
you've mentioned how good the culture is with, with everyone
19:34
that you, that you work with. You know, what kind of culture
19:38
are you trying to build at MUNA, especially when it comes to
19:42
fostering innovation and resilience through the the top
19:45
biotech market that we're in at the moment?
19:47
Yeah. I think one key sort of ethic
19:53
that we've developed at MUNA is sort of to 1 MUNA concept that
19:57
no matter what program you're working on, whether you're
20:00
working on the portfolio of drug discovery and development
20:03
programs are on the mind map platform.
20:06
Are on the GSK collaboration or in some other function like
20:12
finance or HR or or business development.
20:16
It's one for all and all for one.
20:18
And we all own the success and we all are responsible for the
20:22
inevitable bumps in the road and failures that you experience.
20:26
And that one Luna ethic, I think it's held stood as in good stead
20:30
because as you mentioned and as we just chatted about, we're,
20:33
we're quite spread out across the countries and time zones and
20:37
course across the Atlantic. And then the second really key
20:42
feature that has proven I think to be foundational to our
20:49
success is the individual proactivity of the scientists
20:53
and leaders on our various teams.
20:56
So people feeling empowered to speak up and ask questions, to
21:01
look forward and look around the corner to what might be coming
21:04
next and ask questions about that I'm in.
21:08
And to really invest the time and understand if you never
21:12
worked in biotech before, and some of our colleagues have not,
21:15
kind of how the whole enterprise is knit together from leadership
21:19
all the way down to our critically important research
21:22
technicians who fuel, you know, among the best of our best, our
21:27
bench science. So that's sort of teamwork,
21:31
proactive forward thinking, critical thinking, ethic.
21:35
I think it's really part of Muna's DNA.
21:38
It's something that we're very proud of and I certainly AM.
21:41
Yeah, and you've, you've built a fantastic team.
21:44
You're obviously the the series that you raised largest in
21:49
Europe that year. And as you said there, you've
21:51
just recently gone into the clinic.
21:53
So everything you've achieved so far has, has been fantastic.
21:56
What what's next for you guys at MUNA over the next sort of 6 to
21:59
18 months? What was the what's the
22:01
direction that you guys are heading in?
22:03
Yeah. So we of course are looking
22:06
eagerly forward to the outcome of the Phase one trial which
22:11
just began recently and that is being done in a fairly
22:16
traditional way in healthy subjects, single ascending dose
22:21
followed by multiple ascending dose and then an elderly cohort
22:25
which are of course the patients that we hope to serve in Phase 2
22:29
and beyond. And embedded into the trial
22:32
design is a very thorough and foundational exploration of
22:39
biomarkers, some of which came from our preclinical work, some
22:43
of which came from other retrospective analysis we did in
22:47
human clinical samples and colleagues at the Amsterdam
22:50
University Medical Center. So I think over the next,
22:53
certainly six months to 8 months, our efforts will be
22:57
focused like a laser on the successful completion of that
23:01
phase one. We've also recently started the
23:04
chronic toxicology package for our trend 2 small molecule
23:09
agonist, which will be required to take the program to phase two
23:14
or you'll we'll be toasting for, for what we think will be
23:16
something on the ballpark of 12 months.
23:19
So in order to do that, you need a a clean chronic toxicology
23:22
package and we're fortunate that our tox package to date has been
23:27
clean and 28 day GLP tox supporting moving to Phase 1.
23:32
So those are the the key priorities.
23:34
I think in the near term, we have a really robust backup
23:40
chemistry program for our lead asset that will be maturing and
23:44
potentially positioning for additional indications.
23:48
We have our work on mind map. I mentioned in Alzheimer's that
23:52
work is quite mature and the subject of a big pharma
23:56
partnership, but we've expanded the platform to additional
23:59
indications in the last year and work will continue there and of
24:04
course continue to evaluate new targets to come into the
24:09
portfolio and advance our other portfolio programs.
24:12
All very exciting, lots going on on any one day and some, you
24:17
know, some good luck we need to encounter along the way as well.
24:20
But I think we've done just about everything we can do to de
24:25
risk the inevitable uncertainties of being a biotech
24:29
company in neuro and in on top of it in Alzheimer's.
24:34
And I think we're positioned to understand something
24:38
fundamentally important about Trem 2 as a mechanism and about
24:43
the treatment of Alzheimer's disease and move the program to
24:46
phase two, which we're anticipating doing in early
24:49
2027. Yeah, fantastic.
24:52
Look, I, I think even just listening to you talk, you can
24:54
hear the passion come through and everything you've created at
24:57
MUNA. It's obviously a really exciting
24:59
time, Rita. Look, I've, I've really enjoyed
25:01
the conversation. It was great to learn a little
25:04
bit more about your career, especially within research
25:06
academia, what obviously led you into the farmer biotech world
25:10
and then more about MUNA as well.
25:11
So really appreciate you coming on the podcast today.
25:14
I really enjoyed having you on. Thank.
25:16
You. Thank you for having me, George.
25:17
It was my pleasure. No worries at all, take care.