Latest / The BioHub - by Avetix / Episode 145 - Ashley Zehnder - CEO Fauna Bio

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Episode 145 - Ashley Zehnder - CEO Fauna Bio · The BioHub - by Avetix

0:06
So welcome back to their episode of the Bio Hub.
0:08
Today, we're thrilled to welcome on Ashley Zender, a
0:11
veterinarian, scientist and biotech founder who's reshaping
0:14
how we think about medicine. Ashley is the Co founder and CEO
0:18
of Fauna Bio, a company using insights from animal biology and
0:22
genomics to uncover new therapeutic possibilities.
0:26
Ashley trained as a veterinarian, went on to her PhD
0:29
in cancer biology from Stanford University, where she explored
0:33
how studying a wide range of species can unlock breakthroughs
0:36
for human health. So join us today as we'll
0:39
discuss the inspiration behind founding Forna Bio, their
0:43
pipeline, as well as how their fundraising is coming along as
0:46
well. So Ashley, thanks so much for
0:48
coming on. How are you?
0:50
I'm good. Yeah.
0:51
Thanks for having me, Tom. I'm excited to be here to.
0:53
Yeah, it's a it's a pleasure. Look, let's just start off with
0:56
a little bit about your background.
0:58
So you started as a as a veterinarian working with birds
1:01
and exotic species. How did that early experience
1:05
shape the way that you think about biology today?
1:08
And what drew you from clinical veterinary veterinary work into
1:13
cancer biology and genomics? Yeah, it's an interesting story.
1:17
So not, not a common career trajectory.
1:19
So yes, I went into veterinary school always wanting to do
1:23
exotic animal medicine. I had had the opportunity to
1:25
volunteer with clinics when I before I got into vet school
1:28
that did exotic animal medicine. I liked the idea of sort of
1:31
operating on this edge of what we know, right?
1:34
We know a lot about dogs and cats and sort of common animals,
1:36
but not so much about exotics. But they still need care.
1:39
And so it was an interesting area of veterinary medicine to
1:42
become an expert in because you really, like I said right here
1:45
on the cutting edge of what we know about medicine and have to
1:47
adapt what we know from dogs and cats and others into these other
1:50
species. So you become very flexible in
1:53
terms of how you think about medicine, and you also get to
1:56
see the diversity of how different animals present with
1:58
different diseases. Ferrets always come in with
2:02
endocrine diseases. Rabbits get a high incidence of
2:05
reproductive tumors. You know, some species like
2:08
chinchillas hardly ever get tumors.
2:10
And so there's this really stark difference in the biology and
2:13
how different animals present with different diseases and how
2:16
aggressive those diseases progress.
2:18
But a lot of veterinarians like myself are largely clinically
2:21
focused. We don't get a lot of research
2:24
training during that school. It's a very clinically oriented
2:26
curriculum in both schools. And so I didn't have a lot of
2:30
understanding of the molecular underpinnings of the diseases
2:32
that I was treating as a clinician.
2:34
We ended doing a lot of cancer cases.
2:36
We were a tertiary referral center at EC Davis.
2:38
So I saw a lot of complicated cancer cases and thus became
2:41
more interested in cancer and had the opportunity to come down
2:44
to Stanford to do a cancer biology PhD.
2:46
There was a program there specifically for vets who wanted
2:48
to do PhDs and really was understand understand the
2:52
differences in the cancer signaling that occurred across
2:54
species and understanding more about cancer drivers.
2:57
So I did most of that work focused mostly on human cancer
3:00
and really recognized that the same cancer mutations that give
3:03
us cancer are operating in a lot of other species as well.
3:07
And so those those pathways are highly conserved, like most
3:11
genetic pathways and causing disease.
3:12
A lot of those are highly conserved across mammals and
3:15
even beyond. So once I finished up the PhD,
3:18
transitioned into a postdoc, also at Stanford, really working
3:21
now more at the intersection of animal Health and Human disease,
3:24
working with some very large veterinary medical repositories
3:28
and trying to figure out ways to clean up and organize that data
3:30
in such a way that we could align it with, say, human
3:32
medical records and start to look at similarities and
3:34
differences across those clinical presentations.
3:38
It's obviously quite a unique idea that you've you've come up
3:42
with. What was the original spark
3:44
behind found in Fauna bio? And when you and your Co
3:48
founders came together, what strengths did each of you bring
3:50
to the table that made Fauna possible?
3:53
Yeah, found a bio is really the story of its three founders.
3:56
And so I come obviously for more of a clinical translational
3:59
background. My 2 Co founders both have
4:01
backgrounds and expertise in genomics, both with a slightly
4:04
different flavor. So my CTO Linda Goodman did her
4:08
studies and PhD in genomics at Harvard and then became really
4:12
fascinated with what we can learn about evolutionary
4:14
genomics. So how genomes stay the same and
4:16
evolve over time. And it turns out that genes that
4:19
don't change over 100 million years are usually doing
4:21
something important. So can we study those in the in
4:23
the context of disease? But to do that you really have
4:26
to have a really deep lens into the genomes of many, many
4:30
different species so you can understand what it what's
4:32
concerned over time. So she was brought that work
4:35
with her to Stanford to look at evolutionary constraint amongst
4:38
different mammals. My CSO, Katie Grayback, also has
4:43
a PhD in Human Genetics, but rotated in the lab of a
4:45
hibernation researcher named Sandy Martin, who was studying
4:49
the genomics of hibernation. So how does a mammal that has a
4:51
lot of the same genes that you and I do, how are they able to
4:54
almost free themselves from two weeks at a time, rapidly rewarm
4:58
every couple weeks in a way that mimics a heart attack or a
5:01
stroke, do this 25 * / a six month period and come out with
5:05
functioning hearts and brains. To her, that was a much more
5:07
interesting question. And then one more person
5:09
studying human genomic GUA studies.
5:12
So she wrote. She brought that work with her
5:14
to Stanford and wrote an NIH grant to support looking at the
5:16
genealogs of hibernation. And so Linda and I started out
5:20
originally kind of noodling on this idea of how do you build a
5:23
comparative genomics company? We've had the human genome for a
5:25
little over 20 years. We've been able to manipulate
5:28
the genes in mice and rats for a little bit longer than that.
5:31
And we sort of thought we were done right.
5:32
We have the sequence for the human genome.
5:34
We can manipulate these genes in mice and rat models.
5:36
We can solve all the diseases. While the top 10 diseases of
5:39
people haven't changed in the last 10 years, we really just
5:41
added COVID. So what are we missing?
5:45
And so a lot of what we're missing is, well, let's look at
5:47
these same highly conserved genes, but let's look at how all
5:49
the other species are using them.
5:50
And some of them are using in ways that allow them to directly
5:53
resist or reverse diseases that we die from.
5:56
So how do we bring that data in to drug discovery?
5:59
How do we make it usable and discoverable for drug discovery?
6:03
And a lot of the academic labs that are generating this this
6:06
data are not thinking about translation.
6:08
And big pharma companies are not thinking about doing discovery
6:11
and ground scrolls. And so we realized that the
6:13
three of us have this really unique set of expertise.
6:15
My clinical background, Linda's computational genomics and
6:18
really deep background and evolutionary genomics.
6:21
And then Katie's deep expertise and access to samples from this
6:24
one. Remarkable.
6:25
Lee adapted the 13 line ground square, which is a great
6:27
starting point for our discovery process.
6:30
And so the three of us realize that we had this really
6:32
complementary set expertise to identify meaningful trends and
6:36
insights in these species, identify the right species and
6:39
the right time points and the right tissues and then analyze
6:42
them and a really robust computational way to get
6:44
insights out more quickly and. I think another unique thing
6:47
about you guys is that you're both platform and the pipeline
6:51
company and how do you balance building and try to build build
6:55
both at the same time? Yeah, They do support each other
6:58
in interesting ways. And I wouldn't, I wouldn't have
7:01
to trivialize it and say that it's easy because it's not.
7:04
But obviously our assets have come out of our platform.
7:07
It's not always the case with platform companies.
7:09
A lot of times the first assets have come out of somebody's
7:11
academic work and they sort of build the platform around those
7:13
assets. We found our current drug, lead
7:16
drug program with the first version, second version of the
7:18
platform. And I will say that also we've
7:21
been able to do 2 pharma partnerships with the novel data
7:26
and approach that we have with the platform.
7:28
And then the, you know, revenue that we've generated from those
7:31
early platform deals has helped us advance our lead program as
7:35
well as well as the lead program showing a proof point of what we
7:40
can do with the platform. So I think our partnership
7:42
conversations have evolved and matured as they see our pipeline
7:46
evolving and maturing from compounds that we legitimately
7:49
found with the platform approach.
7:51
And so they do feed off of each other and a lot of people at
7:54
Fauna work on both programs. Our head of our therapeutics
7:57
development for 1083 has a large group of consultants who were
8:01
wrapped around that program who were experts in small molecule
8:03
development, but he also is an expert at cardio metabolic
8:06
disease. And so he's the head of our
8:07
internal joint steering committee overseeing the work
8:10
that we do, for example, with Eli Lilly.
8:11
So there's a lot of overlap there.
8:15
And those programs are somewhat complementary in that we're
8:17
working on obesity. We're also working on the type
8:19
of heart failure that's resulting from obesity.
8:21
There's a lot of cardio metabolic mechanisms.
8:25
So you do have to be mindful about bandwidth and resources.
8:27
We've tried to make sure that we're working on things that are
8:30
distinct but yet not wholly different enough that you need
8:35
to build 2 separate companies to do essentially.
8:39
We we've done a really good job, I think, of building teams
8:42
around specific assets. So we have something that has
8:44
differentiated biology. We might have a couple of lead
8:47
point people within Fauna that are leading that internal
8:49
program, but then we leverage outside consultants and experts
8:54
and fractional teams that are experts in that modality or that
8:58
particular disease area that could help move those programs
9:00
forward without hiring a bunch of new people to do that.
9:03
So you just have to be intentional from the beginning
9:05
about we are a platform company, we are going to do therapeutics.
9:08
How do we what kind of expertise do we need to keep in house?
9:11
And then what can we outsource to educated consultants that
9:14
could help with specific programs and not try to pull
9:17
yourself apart. So it's a tricky balance.
9:19
But like I said, the platform is where we found our drug and our
9:22
drug is a great proof point for our platform.
9:24
And so it it does help both ways.
9:27
Yeah, for sure. And just just on the pipeline,
9:29
can you walk us through the lead program and how did that emerge
9:33
from your comparative genomics work that you did as well?
9:36
Yeah, it's a great example of translating the biology into a
9:39
drug. So one of the most profound
9:42
effects that we see in the 13 line ground squirrel that we do
9:45
work on is their their hearts are profoundly protected from
9:48
damage. So as I mentioned earlier, every
9:51
couple of weeks when they're in hibernation, they go from almost
9:53
frozen 4°C up to normal body temperature an hour.
9:57
So the heart rate goes from about 5 beats per minute up to
10:00
two 5300 in a very short period of time.
10:03
It's hard for the oxygen to keep up because they're warming up so
10:06
fast and so their heart gets a little bit of damage every time
10:09
they they warm up and start to cool back down.
10:12
So they evolutionarily then had to devise ways to repair damage
10:15
to the heart that's going to happen every couple weeks over a
10:17
six month period and come out with a normal functioning heart
10:21
and not a scar heart like we would.
10:22
And so we then do is we take heart tissues from these animals
10:26
as they're repairing damage. So they've warmed up and now
10:28
they have to cool back down. That's starting to cool down
10:31
period is where a lot of that repair happened.
10:32
So there's damage has happened to the heart.
10:34
They had to fix it 'cause they're going to drop back down
10:36
into total. So we analyzed RNA sequencing.
10:40
So we're looking a lot of functional genetic studies.
10:42
What are the genes going up? What genes are going down when
10:45
that heart is being repaired in a very precise time point?
10:48
That means we can do discovery with a really small number of
10:51
samples. So our lead program came from a
10:53
study with just 66 zero ground squirrel samples, whereas you
10:57
would often times need thousands or 10s of thousands of humans,
11:00
some of whom may have had good heart outcomes and some of them
11:04
have had bad heart outcomes, to try to find protective alleles.
11:07
Here we're just literally sampling the tissue as it's
11:09
repairing itself. So then we can take those
11:11
genetic signatures. We have a way to map those to
11:14
small molecule compounds. So we have a library where we
11:17
have a library. Small molecules have been used
11:19
to treat human cells, and we get a signature from that.
11:22
And so we can literally just map and say, OK, is there a small
11:24
molecule that, when applied to human cells, gives us the same
11:28
kind of genetic changes that we're seeing in this ground
11:30
squirrel when it's repairing? It's hard.
11:32
So that first foray into mapping small molecules came up with
11:36
essentially the tool compound that formed the basis of the
11:39
chemistry that is now our lead program.
11:41
So we got a tool compound hit. We use that tool compound hit to
11:45
validate in human or sorry in human cardiomyocytes.
11:48
So can we protect human heart cells in the dish from damage
11:50
which they could and then can we protect say heart rats from
11:54
cardiac damage, which it could? And so they given that positive
11:57
vivo data, we then used a medicinal chemistry approach to
12:02
optimize the chemistry and create a novel IP that Nafana
12:06
owns. And that's our development
12:07
compound Fontanity 3, as well as mapping the target of that
12:11
molecule to Human Genetics. So that's always a big part of
12:14
what we do. Let's now look at humans that
12:16
have mutations in this gene that we're targeting.
12:18
Do they have diseases that relate to, for example, heart
12:21
failure, preserved ejection fraction?
12:23
And what we see interestingly is that humans and mutations in
12:26
this target have elevations in pulmonary pressures and have
12:29
changes in what a marker called probe and P that relates to
12:32
cardiac damage and also changes in some of the fuel sources like
12:36
beta hydroxybutyrate that are important during heart failure.
12:39
So there's important functional linkages linking the target of
12:42
this gene to human heart failure.
12:44
And what that's always a part of the discovery that we do is in
12:47
looking at those human genomics, but that's kind of a walkthrough
12:50
of how we went from squirrel tissue to drug and and you know,
12:53
2 minute discussion. I never liked to use the word
12:56
competing because I guess it's always for, it's always for
12:59
patients overall, but who are like the companies that I guess
13:02
are doing maybe similar sort of work to you guys who are, yeah,
13:06
again, not using the word competing, but who are who are
13:08
the other companies that. I think about competitors in two
13:12
different dimensions. I think about people who are
13:14
looking at weird animals and making drugs, and there's a
13:17
small world of companies doing that.
13:20
And I don't consider them really competitors who all work in very
13:22
different spaces. But there's a company called
13:24
Peel Therapeutics that actually got its start looking at why
13:27
elephants still get cancer. Hebrew Peel is Hebrew for
13:30
elephant. That's why the company is called
13:31
Peel. So Josh Schiffman runs that
13:34
company. He's a friend of mine.
13:36
And then there's a company called Paratus Biosciences that
13:38
was started a couple years ago looking at bat biology and
13:41
looking at how they modify their immune system, which is also
13:43
really interesting. So again, all working in very
13:46
different spaces, but all looking at interesting
13:48
approaches. Some people compare us to
13:50
Variant Bio, which is a company that's looking at human
13:54
populations that are naturally resistant to disease.
13:56
Again, I'm friends with that CEO as well.
13:58
We don't really consider ourselves competitive.
13:59
We're not working in the same spaces, but we get talked about
14:02
sometimes in the same circles. So aside from the approach
14:05
comparables within half PEF itself, a lot of those
14:07
approaches are focused primarily on GLP ones, which are sort of
14:11
the new drugs that people are looking at in addition to
14:13
obesity. Are there improvements in
14:15
cardiac outcomes? And some of that data is
14:17
starting to be published. And there's an anticipation that
14:19
those drugs will get labels for half PEF of the coming year
14:22
years. But again, that's really
14:25
affecting the overall metabolic health and not like really
14:27
directly affecting the heart. There are companies that are
14:29
looking at mitochondrial improvements in the heart,
14:33
companies like embryo has a drug that improves mitochondrial
14:36
efficiency. Our drug also has effects on
14:38
improving mitochondrial function, but in a different
14:40
way. Companies looking at myosin.
14:43
So actually looking at an actually a lot of those drugs
14:46
are started out for different kinds of HCM, which is called
14:48
hypertrophic cardiomyopathy. But now they're looking at it
14:51
cannot have an effect on the stiff heart that you get in
14:55
half, half just kind of heart failure we're looking at.
14:58
But those are more functioned of the heart muscle itself.
15:02
And then there are some companies looking at fibrotic
15:04
pathways specifically. So TGF beta and things
15:06
downstream of TGF beta in terms of inflammation, fibrosis, our
15:10
compound acts sort of the Nexus of a couple of these.
15:13
So there's improvements in mitochondrial function.
15:15
It's not a classical mitochondrial target, but it is
15:18
expressed in cardiac mitochondria.
15:20
And we've shown in human cardiac cells that we can improve
15:23
mitochondrial efficiency. And we're also seem to be having
15:26
an effect on sympathetic over regulation.
15:29
So we have sympathetic over activity.
15:31
It can drive damage to the heart over time.
15:33
And this is a target that can reduce some of that sympathetic
15:36
tone that can be elevated due to a bunch of comorbidities that
15:40
give people heart failure. But over time, that kind of
15:43
sympathetic over activation, which is kind of your flight or
15:45
flight response, can cause damage to the heart over time.
15:48
So I said our target sits at a Nexus of a couple of these, but
15:52
those are the approaches that people are largely looking at
15:54
for this type of heart failure. And as you look ahead towards
15:57
2026, what are like the major or the biggest milestones that
16:01
you're aiming for in the next year or so, both scientifically
16:04
and and from a business side of things?
16:07
Yeah, a couple of big milestones.
16:09
We just entered GLP talk studies with that lead program.
16:12
So we'll be finishing those up in the first half of the year.
16:15
And then we'll be starting CMC to start to develop material for
16:18
clinical studies. So we're starting to move for
16:21
the clinic with that first program, which is super exciting
16:23
for us to see that move toward the clinic.
16:26
We are talking with a couple of other big pharma about
16:29
additional partnership deals in adjacent areas, obviously not
16:32
obesity, but there is still quite a bit of interest in
16:35
cardio, renal and immunology and CNS.
16:38
And so we're having already have some meetings scheduled for JP
16:41
Morgan's coming up just around the corner to talk about broader
16:44
discovery programs and some other areas where we have
16:46
tissues and insights but don't have active internal programs.
16:50
So, you know, we're still talking with those folks about
16:52
some additional partnership deals as well.
16:54
And I know you're working towards a Series A raise as
16:58
well. I get how is that going?
17:00
I know how difficult the market's been, particularly over
17:03
the last couple of years or so. How have you guys found the
17:06
kinds of conversations that you're having with with
17:09
investors right now? No, I mean, I don't think it's a
17:11
surprise anybody in the industry.
17:12
It's been a rough year for fundraising.
17:14
I think the market uncertainty, not only just the the global
17:17
markets more generally, but also uncertainty within the FDA and
17:20
regulatory processes have meant that investors have pulled back
17:23
a bit this year. We've been a fortunate that we
17:25
have good partnerships and we have good insiders.
17:28
And so we are pushing for with our GLP talk studies and we're
17:31
already starting to reengage investors.
17:33
You really wanted to come back when we have the GLP talks data
17:35
on hand. So that's what we're pushing
17:37
for, yeah. Just looking back like this is
17:40
obviously your first time CEO job, how has that experience
17:44
been for you so far and what would you say has been the most
17:47
surprising thing you've learned about both leadership or company
17:50
building? Yeah.
17:52
I think I would always like to build a company with Co
17:55
founders. I respect sole founders deeply
17:57
because I don't think I could do that myself.
17:59
I think it's been really extremely helpful to have Co
18:02
founders who are in the trenches with you, who bring, as we
18:04
talked about before, really complimentary not only skill
18:07
sets and expertise, but complementary approaches to
18:10
company building. It was interesting we did our
18:13
one of our anchor investors is a group called True Ventures.
18:15
They are really deep tech investors, but they also do deep
18:19
tech and bio. They are very founder focused
18:23
and actually walk the walk. So they do a founder retreat
18:26
every year for their first time founders to come in a little bit
18:29
early and they they did personality testing on all the
18:32
first time founding cohorts. And it was interesting because
18:35
we took personality tests. I'm blanking on the name of the
18:37
test that we actually took now, but we actually kind of ended up
18:40
on all three corners of this triangle in terms of just how
18:43
our personalities fit together. And so I think finding people
18:46
that can approach problems in different ways, but
18:48
complementary ways is extremely helpful.
18:50
The way that we think about problems is different, but our
18:53
teams then because I lead more of the clinical translational
18:57
therapeutics group of what we do, Linda leads our
19:00
computational group, Katie leads more of our research group.
19:02
There's obviously intersections between all of those and it's
19:05
interesting than building a team under a a group of three leaders
19:09
who are clearly different but complementary and working
19:12
together and, and showing their strengths and weaknesses
19:14
together. Those teams then naturally also
19:17
work together quite well because they see the way that the three
19:21
of us hash out problems and have different some opinions and
19:23
respect each other's opinions on those matters.
19:27
So that trickles down into the ways that we built teams.
19:29
I think what I didn't understand starting and I'm gaining,
19:32
gaining an ever creasing appreciation for now is how much
19:36
of an Arthur is to creating an environment where people could
19:39
do their best work. Everybody does work in different
19:42
ways. Everybody works well in
19:45
different situations and understanding when people need
19:49
focus time, when people when are the right times and what kinds
19:52
of meetings to have to get real work done.
19:55
That's kind of an art that I hadn't appreciated.
19:58
How to run a good meeting is a super boring topic, but
20:00
actually, if you can't run a good meeting, you can't get
20:03
decision and you can't get work done.
20:06
So learning that cadence of how to get the how to motivate
20:09
people right. People want to move up on their
20:10
jobs. They want to be able to stretch
20:12
themselves. How do you give them the freedom
20:14
to stretch themselves while still making sure they get their
20:16
core job done? And sometimes people will flex
20:19
into things that you didn't expect if you give them a bit of
20:21
the freedom to try new things. So learning how to give people
20:25
that freedom to grow into new opportunities while still
20:27
getting the core job done. So it's a lot of people and we,
20:31
we aren't certainly aren't perfect, but we've got a really
20:34
core team of folks now who've been with us getting on to close
20:36
to five years, four and five years.
20:39
That's a really stable group of folks who work really well
20:42
together that are all really driven by the mission.
20:45
So, and also I would say helping people transition from when
20:50
you're a really small company. We were 5 or 6 people for
20:52
several years. We're still small, we're still
20:55
only 20 people. We're not a huge company, but
20:57
going from being an individual contributor to then leading a
20:59
small team, that's a hard transition for some people.
21:02
And some people can't really make that transition.
21:04
And so can people move from I'm an N of 1 to I am an N of four
21:08
and I can share that work amongst that team.
21:12
Learning who can make that transition and who can't is
21:15
important. Nice, and just just to finish
21:17
off, if you were to go back in time and give one piece of
21:20
advice to your 21 year old self, what would it be and why?
21:25
Yeah, it's interesting. My 21 year old self was just
21:27
starting vet school, so I started college year early
21:32
because I end up early enrolling because we moved to Tampa when I
21:35
was in high school as a junior and then I started vet school a
21:39
year early without an undergrad degree.
21:41
So I was two years younger than my vet school colleagues when I
21:43
started. So I think I had that as a
21:46
little bit of a, not a chip on my shoulder, but a little bit of
21:49
a like I was not confident for a very long time 'cause I was
21:55
always felt like I was this like younger kid and a group of older
21:59
kids. Then when I went to college or
22:01
kept my cancer bio PHDI was older, younger kids.
22:05
I guess it switched to just like tell myself to be a little bit
22:09
more confident in my abilities. I think that's the big thing,
22:11
right? I think it's hard when you're
22:12
21, but I was always like a little bit of a sit back and and
22:17
see and very much more passive aggressive in terms of not
22:21
speaking my mind. And so I've I've gotten over
22:23
that to some degree. So I think just tell myself to
22:26
speak up a little bit more, but I think that comes with maturity
22:29
as well. Well, look, thanks so much for
22:31
coming on and helping us out with this.
22:32
It sounds like what you, you're building a fauna is super
22:35
exciting and I'm looking forward to following the, the, the
22:38
progress that you'll make next year as well.
22:40
So yeah, look, thanks for going on, Ashley.
22:42
It was a pleasure and yeah, sounds super exciting, what
22:45
you're building. Yeah, Thank you.
22:47
This is fun. And we're all super excited to
22:49
see everything moving forward and fun.
22:50
It's a fun company to build with people who feel like this is
22:53
their life's work. And so it's a really, it's a fun
22:56
opportunity to be able to build a company like that.