Latest / The BioHub - by Avetix / Episode 191 - Trevor Martin - Co-Founder & CEO Mammoth Biosciences

Transcript

Episode 191 - Trevor Martin - Co-Founder & CEO Mammoth Biosciences · The BioHub - by Avetix

0:06
Today I'm joined by Trevor Martin, Co Founder and CEO of
0:09
Mammoth Biosciences, a company at the forefront of CRISPR based
0:13
gene editing and diagnostics. Since founding Mammoth,
0:17
alongside some of the leading names in genome engineering,
0:20
including Nobel Laureate Jennifer Dudner, Trevor and the
0:24
team have built one of the most recognised platforms in the gene
0:27
editing space. In today's conversation, we'll
0:30
talk through the founding story behind Mammoth, the evolution of
0:33
the platform, the company's approach to AI, machine learning
0:37
engine editing, and where Trevor sees the future of genome
0:41
editing heading over the next decade.
0:44
Trevor, welcome to the podcast. Yeah, thanks for having me on.
0:47
Amazing, and I think it would be useful for our listeners to
0:50
learn a little bit more about your background and what led you
0:53
to founding Mammoth. Yeah.
0:55
So I originally came into college thinking I would be a
0:59
physics major or maybe something more on the engineering side,
1:05
because I think usually biology is taught as kind of stamp
1:08
collecting. It's not taught as something
1:10
where there's kind of like laws of nature that can be figured
1:13
out and replicated or engineered.
1:15
And I was very fortunate that an undergrad, there's a professor
1:20
who started this program to basically trick physicists and
1:24
mathematicians and statisticians and computer scientists into
1:27
becoming biologists. Because especially as more and
1:30
more data is generated in biology and we have more and
1:33
more technologies that can actually manipulate the kind of
1:36
life, for example, like CRISPR, we have really been able to
1:41
treat biology more like physics, more like engineering, more like
1:45
even computer science. So I fell in love with this idea
1:48
that biology is like the messiest possible thing and most
1:51
relevant possible thing we can work on because it codes
1:55
ourselves and we can, you know, help with things like disease or
1:59
famine or just anything that biology touches.
2:03
And that was something that was really, really exciting and new
2:07
to me. So I fell in love with this idea
2:10
of kind of engineering biology and really treating biology like
2:13
a discipline where there are laws of nature that can be
2:16
figured out. So after that undergrad
2:19
experience, went to Graduate School kind of working at the
2:24
intersection of statistics and biology.
2:26
And while I was in Graduate School, I was reading the papers
2:30
that Jennifer was publishing from her lab and that Janice and
2:34
Lucas were were authors on and kind of driving forward and got
2:38
really excited about how there really was a technology that
2:43
allows you not just to kind of understand the biology, but
2:45
actually in turn to engineer it. So it was really kind of frankly
2:50
the obvious place to go next. Yeah, no, that's a really
2:53
interesting story about about your background there.
2:56
And what would you say some of the biggest inflection points
3:00
have been within Mammoth's evolution?
3:03
Yeah. I mean, I think like many
3:05
start-ups, when we we started, we had a pretty broad idea of
3:10
all the different areas of application that this technology
3:12
could be used for because it is quite broad in terms of if you
3:15
can engineer biology, there's millions of things that you
3:18
could do. Even just within therapeutics,
3:22
there's hundreds of thousands of things you could do.
3:25
But we were looking across many disparate fields from
3:27
therapeutics to diagnostics to agriculture to biomanufacturing.
3:32
And I think one of the early inflection points in the journey
3:36
was kind of narrowing that down 1st to therapeutics and
3:39
diagnostics. And then shortly after that the
3:43
COVID-19 pandemic hit. So we probably became best known
3:46
for diagnostics and we were able to do some amazing work
3:50
including things like getting an emergency use authorization for
3:53
a CRISPR based test for COVID. So I think that was one of the
3:58
first important inflection points in the company.
4:01
Then kind of post pandemic, the the next area that we really
4:06
doubled down on was obviously therapeutics.
4:09
We're still big believers in the potential of CRISPR based
4:12
diagnostics. But obviously when you go
4:14
through a pandemic and then come out of it, the market shifts
4:16
substantially. And we're very fortunate that a
4:19
lot of our research on the therapeutic side kind of very
4:21
nicely lined up in terms of timing where we could really
4:25
invest heavily in that side of the business and shift the
4:31
diagnostic side to more licensing and really trying to
4:34
empower others to to use that technology.
4:37
And then on the therapeutic side, probably the biggest
4:40
inflection point is choosing your lead program because at the
4:42
end of the day, you can obviously have a platform
4:46
technology like CRISPR that can do many, many things.
4:48
But one of the most important choices you make is where you're
4:50
going to focus the Canon first. So choosing our our lead program
4:55
in high trail strides and this knocking down the stream called
4:59
APOC 3 definitely was something that there's a lot of internal
5:03
debate about. But I think it's been proven to
5:07
be a great choice more and more over the years.
5:10
And then the next big inflection point we're coming up on is
5:13
actually dosing our first patients with our our lead
5:18
program. And that's really, really
5:20
exciting and kind of shifts the next miles through the company.
5:22
Yeah. I was just about to say, you're
5:24
obviously going into clinic and how does that, you know feel
5:28
internally to get to that stage as the therapeutics business?
5:31
Yeah, well, don't want to jinx it since you're not quite there
5:33
yet, but yeah, it's very exciting to see something that,
5:38
you know, has gone all the way from the bench to the bedside.
5:42
It's kind of crazy to think that, yeah, you'll actually see
5:49
like how that drug that was just like on a napkin essentially,
5:52
like years ago can actually help someone ideally.
5:57
And yeah, it just makes it very, very real.
6:00
And obviously that's like the ultimate motivation for doing
6:03
this. Yeah.
6:04
And I think one thing that stands out about Mammoth as well
6:06
is the focus on diseases with a much broader patient impact.
6:11
Why was it important for the company to think beyond rare
6:14
genetic diseases? Yeah.
6:15
I think our view is that both are important, but people have
6:18
only focused on kind of the more rare side for understandable
6:21
reasons. I think Jean therapy slash, gene
6:25
editing slash, you know, just this whole field is usually seen
6:28
as like really, really kind of like ultra expensive drugs for
6:32
very small populations. And I don't think it has to be
6:36
that way. For example, for our lead
6:40
program, this is an edit that people can benefit from kind of
6:43
regardless of genetic background.
6:46
So it's not something where you have to like sequence the
6:47
patient to say this is a drug that can benefit you.
6:51
It's something where we're kind of able to bring a beneficial
6:55
genetic change to potentially anyone.
6:58
And obviously, even in that situation, you start with the
7:02
smaller populations that are at most risk of developing, in our
7:07
case, things like pancreatitis, so that you can show how
7:10
beneficial the drug is and how safe it is, and then kind of
7:13
expand hopefully the patient populations over time.
7:17
But I think in general, I think both haves have to advance both
7:22
the rare disease and the common disease.
7:25
I mean, there's still thousands of rare diseases that don't have
7:28
any genetic therapy or cure today.
7:34
There's a ton of work to be done on that front, but I think both
7:37
fronts have to advance if we want to realize the full
7:40
potential of genetic. Yeah, of course.
7:43
And So what other indications do you think you'll be able to
7:46
expand into, you know, in the future?
7:49
Yeah. So one of the unique things
7:51
about Mammoth is that we're able to actually because we have
7:54
these things called ultra compact persper systems.
7:56
So these are systems that are like really small like
7:59
physically relative to traditional CRISPR technologies
8:02
like CAS 9, which probably many people have heard of.
8:05
And with these really tiny versions of CRISPR, we can
8:07
actually much more effectively deliver to anywhere in the body.
8:12
So there's a certain areas of the body that are for various
8:16
technical reasons kind of easy to deliver to like the liver or
8:22
blood based diseases where you can actually take the cells out
8:24
of the body and then put them back in and do ex vivo editing.
8:29
And that's where most of the focus of kind of the the field
8:32
is for for that reason. And one of the things we're
8:36
excited about is that we have line of sight to kind of
8:39
expanding beyond that to areas like muscle and CNS because we
8:42
can, we can very effectively leverage kind of various
8:46
delivery methods. And that really unlocks a lot of
8:49
really high impact disease areas like muscular dystrophies for
8:54
example or you know CNS that we all know like Parkinson's and
8:58
Alzheimer's, all these different diseases that are very high
9:01
unmet need. So I think that just being able
9:05
to go beyond the liver generally is very exciting.
9:08
Yeah. And back to kind of the liver
9:11
and cardio metabolic diseases, it's obviously an area with huge
9:15
unmet need globally. How do you see gene editing
9:19
changing the treatment approaches in that space over
9:21
the next decade? Yeah.
9:23
On the cardio metabolic side, I think it'll start with the
9:26
patients that have them as kind of severe phenotypes, whether
9:30
that's like ultra high lipids or ultra high triglycerides.
9:35
And you know, if and when that is shown to be both very
9:39
efficacious but also very importantly very safe, I think
9:43
you will see a push to expand that to larger and larger
9:46
patient populations because I think a people love the idea of
9:51
a true one and done curative therapy.
9:54
And that's very different from kind of how medicine is operated
9:58
traditionally where you're kind of thinking of drugs for the
10:00
rest of your life. For example, recently there was
10:04
some news from Verve who Lily bought or they were talking
10:10
about the kind of first batch of clinical results from their
10:14
program knocking down this gene called PCSK 9, which could have
10:19
really great party metabolic effects for people.
10:23
And I think one thing that was very striking is like how eager
10:28
people were to get access to this medicine when they learned
10:31
this was possible. Because I think there's a big
10:33
debate in the field about like, oh, are people like, do people
10:36
really want a one and done? Or do they want to like take
10:38
drugs for the rest of their life or do they want injections, A
10:40
reporter or all these different things?
10:41
But I think it made it very clear that at least on the the
10:44
patient's side, there's a lot of excitement about kind of being
10:48
truly done with a disease instead of kind of living with
10:51
it perpetuity. I think in general,
10:56
cardiometabolic is a great space because it is one of the major
11:00
drivers of like mortality and bad outcomes, especially in the
11:03
United States. So it's something that you can
11:05
also save the healthcare system a tonne of money if you can
11:09
actually reduce these types of phenotypes.
11:14
So I think it's kind of an obvious place to to start.
11:18
Yeah. And so how does that fit into
11:20
kind of the widest wider discussion around longevity that
11:24
are happening right now? Yeah, depends on the school of
11:27
longevity thought you want to go into.
11:29
But I think especially if you see longevity as like a
11:32
collection of different diseases, then it makes perfect
11:38
sense that you can even think of these as longevity drugs on some
11:41
level, right? If you reduce heart attacks, if
11:43
you are able to increase the quality of life of people later
11:48
in life, I think these are all things that, whether it's
11:51
lifespan or health span, can be very impactful.
11:55
I think in general, the other area that technologies like
11:59
CRISPR can help and longevity is kind of more directly this idea
12:02
of like epigenetic reprogramming and things like that, where
12:05
you're trying to more directly address maybe the causes of
12:08
aging in some more general fashion.
12:12
So there at Mammoth, we're building the technologies that
12:16
can actually do that type of work and actually reprogram, for
12:19
example, the epigenetics of the genome.
12:22
And we're kind of leading up to others to figure out what that
12:24
reprogramming would be, because it's a very hairy problem if
12:27
you've been working, people have been working on for for a while.
12:30
But as that's figured out, I think what's exciting is that
12:33
Mammoth we have built the technologies that could actually
12:35
potentially make those changes so that.
12:39
Yeah. No, that, that's great to hear.
12:41
And kind of shifting to the AI machine learning conversation,
12:45
it's obviously becoming huge part of biotech today.
12:49
How do you think that that impacts within genome editing at
12:52
Mammoth? Yeah.
12:54
I mean, like in the industry, there's multiple levels to it.
12:58
So I think one thing I've noticed is that throughout the
13:00
company, you know, scientists are using these large language
13:04
models to do research to help make slides.
13:08
I mean, just like kind of day-to-day activities.
13:11
It's just like the introduction of like Microsoft Word or Excel
13:14
or something. You start to see it just kind of
13:15
like an everyday work. So that's that's been pretty
13:19
striking to notice. So I think that's something that
13:22
we're we're really focused on. And then more generally, I think
13:26
that Mammoth can benefit immensely from the explosion of
13:30
like all these companies building like different models
13:32
for different parts of the bilateral profits like protein
13:34
folding or like RNA or all all sorts of things.
13:39
And I think that's a good spot for a company to be because the,
13:44
the race to develop the models themselves can be quite like
13:47
brutal and, you know, just requires billions of dollars of
13:50
GPUs. So I think you want to build
13:52
business models that as the models get better, you're in a
13:55
more and more advantageous position because we have
13:58
expertise around leveraging these genetic medicine
14:02
technologies. And the more and more these
14:05
models help us leverage those more quickly, more cost
14:07
effectively, the more and more drugs that we can actually build
14:10
at the end of the day. So I think that whereas a lot of
14:14
industries like you know, SAS or something or maybe being more
14:17
fundamentally disrupted, I think biotech is an industry that can
14:20
fundamentally be enabled and kind of supercharged as these
14:23
models. Yeah, yeah, definitely.
14:25
And looking ahead then, what are you most excited about over the
14:29
next few years, both the mammoth and maybe just the broader gene
14:33
editing field overall? Yeah.
14:35
I think that in maybe many fields, but especially biology,
14:40
everything is kind of slow and then all at once.
14:42
And I think one of the exciting things is that especially for
14:46
certain classes of genetic diseases, I think we're going to
14:48
see extraordinarily rapid progress over the next 5,
14:52
definitely 10 years. For example, liver is one of
14:55
these tissues that is a little bit more accessible in terms of
14:59
in vivo approaches. And I think we're going to see
15:03
just a complete rapid proliferation of genetic
15:07
medicines, OK. So liver is one of these more
15:13
accessible tissues and I think we're going to see a complete
15:15
rapid proliferation of just maybe even medicines for every
15:19
liver genetic disease. Like I think there is a real
15:22
possibility we live in a world 10 years from now where genetic
15:26
disease and liver is not something people have to suffer
15:28
from, which is a crazy statement to make, but I think it
15:31
definitely is something that could be true.
15:35
I think other areas of the body will take a bit longer because
15:39
like we've had to build these like ultra compact systems to
15:42
like really, really get the technology where it needs to go.
15:46
But I think those will be solved as well.
15:48
So I'd say in the kind of short, not short, short, but like 5 to
15:52
10 year timeline, I think there's a real shot that liver
15:55
genetic disease can be fundamentally solved.
15:59
And then over more medium to long timeline, I think there is
16:03
line of sight kind of within our lifetimes that we don't have to
16:07
live with major genetic diseases.
16:11
And I think that's kind of a fundamental shift maybe in in
16:17
how we think about ourselves. Like usually people are like,
16:20
oh, these are the dice that were rolled when I was born and, you
16:22
know, now I have to live with sickle cell or liver chronic
16:27
disease or like a risk of Alzheimer's or whatever it is.
16:31
And if we can actually kind of modify the genome in a safe and
16:35
efficacious way, it really changes the game in terms of not
16:40
having to play the hand here delt at birth.
16:42
And I think that has huge implications for like, health,
16:48
obviously lifespan, longevity, even economic things like
16:52
productivity. Like, you know, imagine how much
16:55
potential can be unlocked for people around the world if
16:58
genetic disease is not something that's kind of weighing down on
17:01
a huge segment of the population to various degrees of severity.
17:07
And also just kind of like the. Yeah, the freedom to not be
17:11
shackled to kind of whatever genetic code you're.
17:15
Yeah, and such an impact on society overall as well, I'd
17:18
assume. Perfect.
17:20
Well, just kind of wrapping us up here for the Biohop podcast
17:23
with the question that we ask all of our guests.
17:26
If you could have dinner with any innovator, past or present,
17:30
who would it be and why? So I think if I had to get
17:33
dinner with any innovator, past or present, Guri would be top of
17:39
the list. I mean, just from first
17:43
principle, she's I think the only person who won a Nobel
17:45
Prize in like 2 different fields.
17:47
It's kind of crazy. And I think one thing I've
17:51
always been enamoured with is kind of going across scientific
17:56
fields and people that are good at that.
17:58
Because like a lot of innovation, which I guess is the
18:00
question is like fundamentally one of the cheat codes to that
18:04
is, is taking an ideal idea from 1 field and then figuring out
18:08
how to apply it to another. Like I've seen just taking ideas
18:13
from physics and then applying them to biology is like a lot of
18:15
low hanging fruit for making real advances.
18:18
So I think kind of, yeah, being able to understand how kind of
18:22
before that was cool quickly and before a lot of.
18:25
Now there's a lot of like interdisciplinary work and it's
18:27
very popular and there's like whole Centers for this like at
18:29
different universities. But back then it really, my
18:31
understanding was not like in so it'd be just interesting to
18:35
understand how she recognised that so early and kind of was
18:39
able to to do that. Yeah, definitely a true
18:42
innovator as well. Well, thank you so much for
18:45
coming on the podcast, Trevor. It was a really great discussion
18:48
and learning more about Mammoth Biosciences and good luck on
18:52
essentially going into clinic as well.
18:54
Yeah, I appreciate it. Yeah, looking forward to it.