July 16, 2026 • 32 mins
Phages are viruses that attack bacteria. People have been using phages to treat infections for over a hundred years, but in most cases they just don't work as well as antibiotics.
Paul Garofolo is the co-founder and CEO of Locus Biosciences. His problem is this: How do you genetically engineer phages to be more effective at curing disease?
In this episode, Paul explains:
- Why wild phages never completely wipe out a bacterial infection
- How to engineer phages with CRISPR to kill bacteria more effectively
- The clinical trial testing phage therapy for chronic, recurrent UTIs
- Why persistent bacteria may contribute to autoimmune conditions like Crohn's disease
- How to use robots and AI to create phage cocktails from wastewater
Connect with us:
- Follow Jacob Goldstein on LinkedIn, X and Instagram
- Email us at problem@pushkin.fm
- Follow Pushkin on Instagram, LinkedIn or X
- Listen to Jacob’s other show, Business History
- To listen to the show early and ad free, sign up for Pushkin+
See omnystudio.com/listener for privacy information.
Listen
Watch
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:15):
Pushkin. I love phages. Phages are viruses that attack bacteria.
Phages are unimaginably abundant, a trillion phages for every grain
of sand on Earth, according to one estimate, which what
(00:36):
does that even mean? Qualitatively? It means phages are all
around us, they are inside of us, They're essential to
life on earth, and they may help to improve human
health in a profound way. I'm Jacob Goldstein. This is
(01:03):
what's your problem? And my guest today is Paul Garifolo.
He is the co founder and CEO of a company
called Locust Biosciences. Paul's problem is this, can you use
genetically engineered phages to cure disease? People have been trying
to use phages to cure infections for over one hundred
(01:23):
years now, but in most cases, naturally occurring phages just
don't work as well as antibiotics as drugs. Phages reduce infections,
but they often don't wipe them out entirely. So Paul
and his colleagues are taking a different approach. They're genetically
engineering phages to make them better at killing bacteria. For now,
(01:45):
the company is testing its first phage based drug in
patients in combination with antibiotics. But Paul says, the long
term dream is bigger than that.
Speaker 2 (01:56):
So we actually have been trying to figure out how
to selectively remove bacteria from the human body without touching
any of the good bacteria that's in there, and we
believe that that is a key to longevity of human life.
(02:16):
We're starting with trying to replace antibiotics, but we believe
that any number of diseases in the human body or
actually the body's reaction to inflammation from bad bacteria getting
in there and not leaving. And so that's what Locus
is trying to do.
Speaker 1 (02:36):
That's the big dream. There's a narrower dream that I'm
also interested in, yes, and that maybe a question that
gets at the narrow dream is what are the limitations
of antibiotics that you're trying to address.
Speaker 2 (02:52):
I think there are two things that are wrong with antibiotics.
So one that most people are very, very familiar with
is resistance is now everywhere, and so effectively we're beginning
to see exponential increases in drug resists from almost all
mainstream antibiotics, if not all. So there's sort of a
(03:15):
math problem from here. At some point none of them
work and the further up in strength you move in antibiotics,
the more toxic they are to your body. And so
if you're really sick and you have to go on
a really strong antibiotic, the antibiotic itself can be your demise.
(03:37):
So that's one thing. Another example might be people with
recurrent ear infections or recurrent bladder infections end up going
onto frequent batteries of antibiotics, say, you know, starting at
fifteen days, but eventually getting the things like thirty days
or forty five days of low volumes, and that can
(03:59):
wreak havoc on your body. You know, it could basically
destroy the balance in your microbiome. And you can have
things that are long ranging side, like having to go
on substantially simplistic diets for a long period of time
because your intestinal track can't handle the variety of food
that it likely needs for longevity. So those are just
(04:22):
a couple of examples.
Speaker 1 (04:24):
Why my phages help to solve this problem.
Speaker 2 (04:28):
So we think that phases are one of the most
unique and creative ways of getting into the human body
to selectively attack a very specific bacterial pathogen or pathobian
of interest, and only that particular target so I'm sure
(04:51):
you've heard about precision medicine on the gene editing side
for human cells that might be able to fix some
of the world's roughest diseases. But on the bacterial side,
precision medicine is quite new, And the idea of using
phases as a delivery vector is essentially centering around the
(05:16):
fact that they're exquisitely unique to the bacteria that they've
evolved to infect. And so I think the largest, most
abundant and oldest biological organism on the planet besides bacteria
is faish.
Speaker 1 (05:36):
Yeah, that's amazing, right, Like the Earth is full of
phases in the sea. When every day half of the
bacteria and the sea get killed by stages or something like,
it's wild, right, It's like it's incredible.
Speaker 2 (05:48):
Yeah, they say that half the bacteria on the planet,
soil sea in Europe.
Speaker 1 (05:53):
Every day, Like it's happening all around us. It's happening
inside our bodies, right, there are phases that naturally occur
inside our.
Speaker 2 (05:58):
Bodies, and bacteria actually double at a very similar pace, right,
So that this is one of nature's oldest and most
established ecosystems.
Speaker 1 (06:10):
And this is an old idea it's super exciting when
you hear it and they're like, oh wait, people have
been trying to attack bacterial infection with phages for literally
like one hundred years, right, and I haven't got that
far with it. It sounds perfect. Why hasn't it worked
that well so far?
Speaker 2 (06:29):
I think there are probably two or three reasons of note.
One is that people essentially since i'd say a century
ago when they were discovered, they use wild type phases,
meaning they don't do any type of enhancement to that virus,
(06:51):
They don't change the genome in any way. They simply
search for one that is effectively a good killer in
an academic lab, and then they take that killer and
they put that into the human body expecting similar results.
And you can see efficacylevels of those types of what
(07:12):
we call wild type phase treatments in anywhere from fifty
to maybe even sixty five maybe even in best cases
seventy percent range, which you would say, well, that sounds decent,
pretty good, But antibiotics have traditionally, up until when resistance
(07:32):
has started to come into fray, those typically work around
or above ninety five percent. So the efficacy difference between
those two wild type phases and antibiotics is just so stark.
In the days of the Cold War, antibiotics were not
really available to people that were behind the Iron Curtain,
(07:55):
and so face there be actually continued in many places
inside Georgia, Russia, et cetera, and advanced into treatment centers
that really were gear around a single phage for a
single bacteria. And what that leads me to this sort
(08:16):
of the second I think not shortcoming, but just natural
component of phase, which is an individual PHASEE to go after.
Let's say, a large population of bacteria in the human
body will begin to see resistance.
Speaker 1 (08:33):
So that's the story of as you said, wild type
phasi is naturally occurring phasis, you're doing something much more
twenty first century right in a few ways. So we
should introduce another sort of idea slash piece of jargon now, right,
which is crisper cast three. People are used to think
(08:53):
of crisper as like the gene scissors, right. I think
people are relatively familiar with that, But this is a
variant that is like the gene shredder, right, as opposed
to a scissors.
Speaker 2 (09:03):
Yes, it works like essentially a pac Man if you
remember the old arcade game. So it essentially makes a
small nick in one strand of the DNA of the
double helix, and then it choose that strand back by hundreds,
if not thousands of base pairs to the point where
it renders that that cell dead and by no means.
(09:25):
And I think this is an evolution of our company
and perhaps many others. Chrisper systems are not the only
thing that you can engineer into a phage, Peptides, other enzymes,
all kinds of things.
Speaker 1 (09:36):
Oh interesting, but that's I mean, just to be clear,
Like the I call them drugs, they're drugs, rightugs. The
drugs that you have in clinical trials are combining crisper
cast three with a phage, right, Yes.
Speaker 2 (09:50):
Our lead asset is an E. Coli based product. It
has six phases inside of that product, so it's a
cocktail of phases and the majority of those phases are
engineered to carry the entire crisper castori construct inside.
Speaker 1 (10:09):
So it's basically six different phases, each of which you've
engineered to put on this gene shredder gene pac man.
So the ideas the phases go into the infecting cells,
the E coalie the bacteria, and then the Crisper eats
up the DNA of those bacteria, thus killing the bacteria.
That's the basic idea.
Speaker 2 (10:29):
That's the basic idea.
Speaker 1 (10:30):
So basically the idea is if you do a a
bunch of different phases and b add to them something
like Crisper casts three that makes it extra deadly, then
you can clear the infection rather than just reducing.
Speaker 2 (10:44):
Correct.
Speaker 1 (10:45):
And so now you are running a clinical trial on
women with recurrent urinary tract infections? Is that right?
Speaker 2 (10:53):
Correct?
Speaker 1 (10:54):
So tell me about that trial, like, where is it,
what's happening, what's the you know, what's the outcome?
Speaker 2 (11:01):
Yeah. So we just does patient two hundred and twenty
nine yesterday. We've got probably two hundred and eighty eight
to maybe three hundred and eight patients that we're going
to dose. And the idea is that it would not
only deal with the acute infection that you're getting hit
(11:22):
with right now, but it actually either eliminates or dramatically
reduces the number of recurrent infections that you'll see in
the future.
Speaker 1 (11:32):
Yeah, So tell me about like recurrent UTI as a problem.
Speaker 2 (11:37):
Inside the United States alone, over ten million people get
recurrent infections, of which two million of that patient block
get multiple recurrences. Once you get into a pattern of
having multiple recurrences, it's very difficult to get rid of those.
Many patients evolve through decades into a state of colonization,
(12:00):
which just simply means that that bacteria embeds itself somewhere
in your body and reinfections occur. You know, maybe for
some a few times a year, but for many five
six times a year.
Speaker 1 (12:12):
And how are you delivering the face treatment?
Speaker 2 (12:14):
So we have an intraor ethral delivery into the bladder,
So we use a catheter, we avoid the bladder of
its content, and then we reverse flow the drug product
into the bladder, and in the process we also expand
the bladder to make sure that the bladder wall is coded,
and we hold the drug product there for about forty
(12:34):
to fifty minutes before the patient's void. Again, we do
that on the first day and the second day, and
then simultaneously we have an intravenious backdrop that really is
meant to try to get to the kidneys, and we
do that on day one, two, and three, So the
total time and duration is three days.
Speaker 1 (12:54):
So this is an intense treatment. This is like your
uti would have to be extremely bad to want to
do this.
Speaker 2 (13:02):
Frankly, you're in that two million patient population. And you know,
if you had think about it this way, if you
had a urinary track infection that was so bad that
you had to stay home from work for three or
four days until the antibiotics that you got called in
for you kicked in, and then you were still under
the weather for another six or seven days, and then
(13:23):
at the end of that period, within a month to
two months, you got another one, and those infections just
in fact, when we talk to urologists and we talked
to eurogynecologists, they say that this particular infection is the
one that they feel the worst about for their patients
over anything that they deal with, because there's nothing that
(13:45):
they can really do about them except for treat them
with antibiotics as the occurrences happen, and just keep giving
them antibiotics every time they happen.
Speaker 1 (13:55):
What are the risks? What are the risks associated with
the fish treatment?
Speaker 2 (14:00):
So we have not seen any crazy averse events, but
the amount of viral particles that we put it into
the body, some patients can get low grade fever, some
patients can get a little nauseous.
Speaker 1 (14:16):
You're giving people a virus, right.
Speaker 2 (14:18):
You're giving a lot of virus.
Speaker 1 (14:21):
So when are you going to know if phase plus
antibiotic works better than antibiotical one.
Speaker 2 (14:29):
So we should be finished dosing. We believe we'll be
finished dosing sometime in the late fall to early winter,
and then within ninety days from that last dose we'll
have the data.
Speaker 1 (14:42):
So next less than a year. You should know.
Speaker 2 (14:45):
Definitely less than a year.
Speaker 1 (14:47):
So this UTI study is the one that's farthest along
for you, what else do you have in clinical trials?
Speaker 2 (14:55):
So we have applied for an ID for a Crone's
asset to try to essentially have an oral product that
is similar to the UTI product but works more towards
adherent invasive equal LIE, which is in many areas of medicine,
(15:16):
considered to be at worst associative at best causal of
Crohn's disease. In addition to that one, we're very close
to being able to submit an I and D for
this hospital acquired pneumonia asset, and that should be if
we're on time, that one should get approved before the
(15:37):
end of the year. So in theory, by the end
of this year, in the beginning of next year, we
would have three to four assets that we're moving through
the clinic.
Speaker 1 (15:46):
And an asset is a drug. An asset's a drug,
a drug that you own. That's why it's an asset
for you.
Speaker 2 (15:51):
Well, in some cases partnered, but yes, one that we own.
Speaker 1 (15:55):
Or co own. Yeah, somebody owns. We'll be back in
just a minute. Tell me about how you're using AI
(16:17):
at your company.
Speaker 2 (16:18):
Yeah, so we use a what we call AI driven robotics,
and so we discover phase at a volume I don't
think anybody in the past has used. And then when
we get those phage isolated, we sequence them, we run
full characterization on them, and then we start running them
(16:38):
through prediction engines that help us figure out what payloads
to put into their genomes and which ones of those
should go together and do a fixed drug.
Speaker 1 (16:48):
So, so let me just take a sec to understand
that the prediction engines part, that second part that sounds
like AI. But what's the robot part and how is
it different than you know, what happens in a normal lab.
Speaker 2 (17:01):
Well, in a normal lab, you have a pipette, yeah
kind of, Yeah, you have a little thumb thing that
like depress and yeah, so you know discovering phases using
sort of your regular old run of the mill.
Speaker 1 (17:16):
So what what So, okay, what are you doing.
Speaker 2 (17:19):
We're using hundreds, if not thousands, of ninety six well
plates with the robot running twenty four hours a day,
essentially looking at wastewater that we pull from all fifty
states outside of international airports.
Speaker 1 (17:36):
Oh, you're doing outside of international airports because it's a
more biodiverse sample, Like hundred percentages are flying in from
all over the world in people's bodies in your samp
Like that. I love that.
Speaker 2 (17:48):
Yeah, that's really cool.
Speaker 1 (17:49):
Would you say wastewater like you just go to like
the sewer, Like, how do you actually do this?
Speaker 2 (17:54):
You reach out to the municipalities and you set up
opportunities to pull them. And I mean in the early
early days, we would go out there and we'd knock
on the door and we'd askay can we do this?
And in a lot of case as you can.
Speaker 1 (18:10):
And what's the order of magnitude of like how many
different phases your your system is going through?
Speaker 2 (18:17):
So we have found it probably eighty five hundred uniquely identified,
fully characterized phases against ninety nine different bacterial targets. So
less size and scale that most academic labs, if not
any academic lab could ever match.
Speaker 1 (18:35):
So then so that's that's the robot stage. And then
you were saying, you move on to the to the
kind of AI stage. What's that?
Speaker 2 (18:43):
So you maybe the best way to think about is
it can work a little bit like Netflix. So if
your you know, you watch a particular type of movie
and there's a little algorithm behind the scenes that tries
to figure out, well, what's the next best movie that's
like that that you might want. And so we essentially
(19:04):
apply very similar models to the sequenced information that we
have on each of these unique phases, and we start
to try to figure out, really by evaluating quadrillions of
different options of pairing hundreds of not thousands of phase together,
which one which four or five, six or seven of
these go best together?
Speaker 1 (19:24):
So you want them to be complementary. You're targeting you're
targeting some particular bacteria, and you're like, okay, give me
the best cocktail correct AI.
Speaker 2 (19:33):
Yep. And then once it says try these top three,
we go make them and then we grow it up
and you know, manufacture small quantities of it, and then
we test them out.
Speaker 1 (19:43):
And is that how you got the cocktails that are
in trials now.
Speaker 2 (19:46):
The one that we have that's in trial now probably
was a bit more manual because it's our first asset
and it's probably built like seven years ago. The two,
the three that we have that are coming this year,
we're all built using that approach. So we're excited about
the second generation assets that are going in.
Speaker 1 (20:08):
So so let's talk more long term, Like, let's talk
about the sort of phase dream I've heard you talk about,
you know, the potential that the kinds of things you're
working on might go beyond what we think of as
infectious disease someday. Tell me about the sort of big,
big dream for phase treatment.
Speaker 2 (20:28):
I think crones sits in that arena for us. So
Crone's disease is a immune disorder that essentially your body's
immune system mistakes something in your intestinal track for an infection,
and it targets your own intestinal organs and eats away
(20:49):
at them to the point where you have small lesions
that are actually in your intestinal lining. And what we
know how to do in the field of medicine is
essentially turned down the intensity of the attacking.
Speaker 1 (21:05):
So it's an autoimmune disorder. It's not thought of as
infectious disease. Correct, So where does where does face therapy
come in?
Speaker 2 (21:15):
In many circles of ib D, it's thought that bacteria
is what the immune system is attacking.
Speaker 1 (21:23):
And IBD is inflammatory bowel disease. It's like that crones
is one of.
Speaker 2 (21:27):
Your crones colitis variant forms of those anything that essentially
diverticulated these types of things consider essentially intestinal organ disorders.
There's a big umbrella term for IBD. And so many
scientists believe that there are bacteria that gets stuck in
(21:48):
there and are non transient, and it's those bacteria that
get stuck in there and somehow adhere to the intestinal walls,
that that is what the immune system is attacking.
Speaker 1 (22:01):
And that makes your immune system freak out and start
attacking not just those cells but the bodies own cells.
Speaker 2 (22:07):
Correct. And so are drugs. And what we think is
the holy grail of medicine is to be able to
use phage encoded with payloads that can eat through either
the biofilms, mucle layers or macrophage layers that protect those
intracellular pathogens that our drugs would be able to get
there precisely and kill just those pathogens, thereby causing the
(22:33):
immune system to calm down and to potentially heal that
patient with something that's curative.
Speaker 1 (22:41):
And just to be clear, is it the case that
antibiotics just don't work for the particular the bacteria in
the setting that you're describing.
Speaker 2 (22:50):
Antibiotics are known to not be able to kill intracellular pathogens.
They can't transit into the human cells to kill the human.
Speaker 1 (22:58):
Cells, which is why they don't kill us.
Speaker 2 (23:01):
Presumably why antibiotics don't kill us. Yeah, presumably, I mean,
that's one way to look at it.
Speaker 1 (23:08):
Absolutely, yeah, Yeah, And this is a trial that you're
hoping you're hoping to sort of start a clinical trial
based on this hypothesis. You said in the next year
or so, we hope.
Speaker 2 (23:19):
To, We hope to. We still need to raise fund
specifically for that one.
Speaker 1 (23:23):
I believe it less the way you say we hope to.
Speaker 2 (23:26):
Yeah, that when you're running a company like this, you
tend to go where your contracts and partnerships are, and
right now we have contracts in three of four areas,
and so of course we're busy working on all three
of those, and we hope to add the fourth.
Speaker 1 (23:41):
So what's the bigger idea here? Like, we kind of
went far into the weeds on crumbs, But what is
the bigger idea for you know, if you're right, like,
what is the big hope for phaci therapy and whatever
ten years or something.
Speaker 2 (23:53):
So I'll start high level and go down into that.
Inflammation in the human body is not good. It causes
many diseases without question, things like rumtory torte is potentially
neuro disease is Things related to dementia, Parkinson's, etc. Like
when inflammation occurs in certain sections of the body, bad
(24:16):
things happen. Our hope for this platform is that it
can reach into the human body via precision medicine and
pull those pathogens or pathobians out.
Speaker 1 (24:28):
Is the underlying hypothesis that this sort of mysterious systemic
inflammation is caused by particular kinds of bacterial infection.
Speaker 2 (24:36):
Yes, many pathogens that are in the body are bad actors.
They're non transient, and the immune system is likely attacking
those non transient bad actors. And so if you have
a platform that can remove those bad actors, you likely
also get the benefits of being able to improve the
(24:57):
health of the human body, and that we believe will
do things like increase the lives of most people in society.
Or if you're genetically predisposed to a disease, you may
be able to prevent the onset of that disease for
a longer period of time. If you're genetically predisposed to
a disease, you might be able to lessen the severity
(25:20):
of that disease on your life. A good example might
be rheumatory authritis. So if you remove pathogens that either
aggravate or cause rhumatory authritis, can you help that patient
with their symptomology. Can you decrease the pain that's associated
in your joints with that disease by decreasing the amount
(25:41):
of pathogens that you actually have in the body. We
believe that that is a theory that is absolutely worth
going after trying to figure out. And many people don't
really realize this, but a lot of medicine is built
on suppression. GOLP wants, autoimmune drugs. These things are basically
(26:05):
shutting something down in the body to help a patient.
They're not actually dealing with causes, and so hopefully also
then we can start to talk about cures. But certainly
if we're able to show direct causal relationships between certain
(26:26):
pathogens that are in the body and improvement and disease symptomology,
I think we're onto something really, really big.
Speaker 1 (26:37):
We'll be back in a minute with the liking round.
What's your favorite phase?
Speaker 2 (26:51):
My favorite PHASEE?
Speaker 1 (26:53):
Yeah?
Speaker 2 (26:55):
Actually I really enjoy thinking about macrophages.
Speaker 1 (26:59):
Oh, the giant ones that they didn't even know where
virus is because they're so big.
Speaker 2 (27:03):
Yeah, they tend to evolve really fast and move around
on you, so it makes it a little bit interesting
to figure out out how to actually pin one down
and keep it from doing that when you don't want
it to. But the possibilities of what you can load
into a phase, the size of the payload that you
could get in there, if you could replicate it, that's
pretty exciting.
Speaker 1 (27:23):
So as a phase engineer, you're like, if we could
tame that guy, we could stick anything in there.
Speaker 2 (27:27):
Yeah, I guess it'd be like taming a really big bull, right,
Like what we get from that? I think the idea
of being able to put all kinds of different peptides
or other enzmatic tools into a phaseI and getting it
very specifically into a certain part of the body and
then having it in c too manufacture that payload right
(27:47):
at the site where you want it. It's pretty fascinating
as someone who's been in the industry for a number
of decades. There's tons of good drugs that are on
the shelf because of things like half life considerations, where
it just doesn't stay alive and active long enough.
Speaker 1 (28:03):
Huh.
Speaker 2 (28:04):
But if you're manufacturing it in the body right where
you need it with a phage, what can you do
with those peptides that have long since been on the shelf.
So I think there's some really cool things you can
do with phases that are larger that might be able
to carry some cool stuff.
Speaker 1 (28:21):
I heard you say that part of the reason you
started a company was because you don't have a PhD.
And you realize that in bigger companies there was just
a ceiling on what you could do without a PhD.
And I'm curious, have you found any advantages of not
having a PhD. Does it give you any kind of
a inside or edge that you might not have if
(28:42):
you did have one.
Speaker 2 (28:43):
I mean, you can ask dumber questions of your team
and get away with it. It sort of like why
do you think that I don't understand? Explain that to me.
Speaker 1 (28:52):
That's actually I will say, that's my whole game. That's
like my job is. It's like I don't understand that.
Explained it to me.
Speaker 2 (28:58):
I also think that it gives us. It gives our
culture inside of our company a bias towards more execution.
And not that we're any less curious about scientific discovery,
but once you pass a certain point where you're moving
into the clinic and through the clinic, it's time to execute,
and so you stay focused a little bit better.
Speaker 1 (29:19):
Right. You're an engineer by training, right, that's a very
engineering mindset. Right, let's build a thing.
Speaker 2 (29:25):
Yeah, I'm a project manager by background. I'm a project manager.
That's what I was. I guess raised doing is running
huge projects.
Speaker 1 (29:34):
So you've been in biotech for what thirty more than
thirty years, right, which is ye a long time. And
I'm curious if you sort of look over the arc,
if you go back to when you were starting, I'm
curious what's surprising to you, Like, what has done better
than you expected? What has done worse?
Speaker 2 (29:54):
That's a really no one's ever asked me that one before. Okay,
I mean, I think on the better side, I really
have been in awe and excited about cures I started.
If you said, hey, we're working on a cure, people
would look at you and you'd immediately be discredited.
Speaker 1 (30:17):
So what can we cure now that we couldn't cure
when you started?
Speaker 2 (30:20):
I don't think you necessarily have all of the cures
for things like do Chanes or Parkinson's or Alzheimer's that.
Speaker 1 (30:28):
Are definitely not for those, But what can we cure?
Speaker 2 (30:32):
I think they're I think they're coming. And that's that's
my answer to your question of what's really cool about
biotech the hard parts, the parts that maybe aren't so
fun is I think we had just a huge bullet
of garbage ideas that flooded into the industry post COVID.
The amount of money that came into the industry post COVID,
(30:54):
the craze around SPACs. It basically drained all the talent
into a bunch of BS companies, and it took a
couple of years for that to flood out.
Speaker 1 (31:03):
The curse of too much money. It's funny people mention
that more often than I would have thought.
Speaker 2 (31:09):
In an industry that's used to creating four hundred companies
per year. You don't want to create four thousand for two.
And that's not you just don't have the talent enough
in the executive and leadership ranks to hold that. And
where you get that from as your service partners, you're
your vendors, and then your vendors don't know what they're doing.
(31:30):
And so we had to live through that. I think
we're through that. I actually think we're on the other
side of that, which is I guess time will tell
as we see what actually breaks through.
Speaker 1 (31:46):
Paul Gariffolo is the co founder and CEO of Locust Biosciences.
Please let us know what you think of the show.
Do you want to hear more of, which you want
to hear less of? Would you go guest ideas? You
can email us at problem at pushkin dot fm. I
read all the emails. You can also find me on
x LinkedIn. Do appreciate all the messages that we get.
(32:12):
Today's show was produced by Gabriel Hunter Chang and Trina Menino.
It was engineered by Hans Dale She and edited by
Lydia Jean Kott. I'm Jacob Goldstein and we'll be back
next week with another episode of What's Your Problem,
Pushkin. I love phages. Phages are viruses that attack bacteria.
Phages are unimaginably abundant, a trillion phages for every grain
of sand on Earth, according to one estimate, which what
(00:36):
does that even mean? Qualitatively? It means phages are all
around us, they are inside of us, They're essential to
life on earth, and they may help to improve human
health in a profound way. I'm Jacob Goldstein. This is
(01:03):
what's your problem? And my guest today is Paul Garifolo.
He is the co founder and CEO of a company
called Locust Biosciences. Paul's problem is this, can you use
genetically engineered phages to cure disease? People have been trying
to use phages to cure infections for over one hundred
(01:23):
years now, but in most cases, naturally occurring phages just
don't work as well as antibiotics as drugs. Phages reduce infections,
but they often don't wipe them out entirely. So Paul
and his colleagues are taking a different approach. They're genetically
engineering phages to make them better at killing bacteria. For now,
(01:45):
the company is testing its first phage based drug in
patients in combination with antibiotics. But Paul says, the long
term dream is bigger than that.
Speaker 2 (01:56):
So we actually have been trying to figure out how
to selectively remove bacteria from the human body without touching
any of the good bacteria that's in there, and we
believe that that is a key to longevity of human life.
(02:16):
We're starting with trying to replace antibiotics, but we believe
that any number of diseases in the human body or
actually the body's reaction to inflammation from bad bacteria getting
in there and not leaving. And so that's what Locus
is trying to do.
Speaker 1 (02:36):
That's the big dream. There's a narrower dream that I'm
also interested in, yes, and that maybe a question that
gets at the narrow dream is what are the limitations
of antibiotics that you're trying to address.
Speaker 2 (02:52):
I think there are two things that are wrong with antibiotics.
So one that most people are very, very familiar with
is resistance is now everywhere, and so effectively we're beginning
to see exponential increases in drug resists from almost all
mainstream antibiotics, if not all. So there's sort of a
(03:15):
math problem from here. At some point none of them
work and the further up in strength you move in antibiotics,
the more toxic they are to your body. And so
if you're really sick and you have to go on
a really strong antibiotic, the antibiotic itself can be your demise.
(03:37):
So that's one thing. Another example might be people with
recurrent ear infections or recurrent bladder infections end up going
onto frequent batteries of antibiotics, say, you know, starting at
fifteen days, but eventually getting the things like thirty days
or forty five days of low volumes, and that can
(03:59):
wreak havoc on your body. You know, it could basically
destroy the balance in your microbiome. And you can have
things that are long ranging side, like having to go
on substantially simplistic diets for a long period of time
because your intestinal track can't handle the variety of food
that it likely needs for longevity. So those are just
(04:22):
a couple of examples.
Speaker 1 (04:24):
Why my phages help to solve this problem.
Speaker 2 (04:28):
So we think that phases are one of the most
unique and creative ways of getting into the human body
to selectively attack a very specific bacterial pathogen or pathobian
of interest, and only that particular target so I'm sure
(04:51):
you've heard about precision medicine on the gene editing side
for human cells that might be able to fix some
of the world's roughest diseases. But on the bacterial side,
precision medicine is quite new, And the idea of using
phases as a delivery vector is essentially centering around the
(05:16):
fact that they're exquisitely unique to the bacteria that they've
evolved to infect. And so I think the largest, most
abundant and oldest biological organism on the planet besides bacteria
is faish.
Speaker 1 (05:36):
Yeah, that's amazing, right, Like the Earth is full of
phases in the sea. When every day half of the
bacteria and the sea get killed by stages or something like,
it's wild, right, It's like it's incredible.
Speaker 2 (05:48):
Yeah, they say that half the bacteria on the planet,
soil sea in Europe.
Speaker 1 (05:53):
Every day, Like it's happening all around us. It's happening
inside our bodies, right, there are phases that naturally occur
inside our.
Speaker 2 (05:58):
Bodies, and bacteria actually double at a very similar pace, right,
So that this is one of nature's oldest and most
established ecosystems.
Speaker 1 (06:10):
And this is an old idea it's super exciting when
you hear it and they're like, oh wait, people have
been trying to attack bacterial infection with phages for literally
like one hundred years, right, and I haven't got that
far with it. It sounds perfect. Why hasn't it worked
that well so far?
Speaker 2 (06:29):
I think there are probably two or three reasons of note.
One is that people essentially since i'd say a century
ago when they were discovered, they use wild type phases,
meaning they don't do any type of enhancement to that virus,
(06:51):
They don't change the genome in any way. They simply
search for one that is effectively a good killer in
an academic lab, and then they take that killer and
they put that into the human body expecting similar results.
And you can see efficacylevels of those types of what
(07:12):
we call wild type phase treatments in anywhere from fifty
to maybe even sixty five maybe even in best cases
seventy percent range, which you would say, well, that sounds decent,
pretty good, But antibiotics have traditionally, up until when resistance
(07:32):
has started to come into fray, those typically work around
or above ninety five percent. So the efficacy difference between
those two wild type phases and antibiotics is just so stark.
In the days of the Cold War, antibiotics were not
really available to people that were behind the Iron Curtain,
(07:55):
and so face there be actually continued in many places
inside Georgia, Russia, et cetera, and advanced into treatment centers
that really were gear around a single phage for a
single bacteria. And what that leads me to this sort
(08:16):
of the second I think not shortcoming, but just natural
component of phase, which is an individual PHASEE to go after.
Let's say, a large population of bacteria in the human
body will begin to see resistance.
Speaker 1 (08:33):
So that's the story of as you said, wild type
phasi is naturally occurring phasis, you're doing something much more
twenty first century right in a few ways. So we
should introduce another sort of idea slash piece of jargon now, right,
which is crisper cast three. People are used to think
(08:53):
of crisper as like the gene scissors, right. I think
people are relatively familiar with that, But this is a
variant that is like the gene shredder, right, as opposed
to a scissors.
Speaker 2 (09:03):
Yes, it works like essentially a pac Man if you
remember the old arcade game. So it essentially makes a
small nick in one strand of the DNA of the
double helix, and then it choose that strand back by hundreds,
if not thousands of base pairs to the point where
it renders that that cell dead and by no means.
(09:25):
And I think this is an evolution of our company
and perhaps many others. Chrisper systems are not the only
thing that you can engineer into a phage, Peptides, other enzymes,
all kinds of things.
Speaker 1 (09:36):
Oh interesting, but that's I mean, just to be clear,
Like the I call them drugs, they're drugs, rightugs. The
drugs that you have in clinical trials are combining crisper
cast three with a phage, right, Yes.
Speaker 2 (09:50):
Our lead asset is an E. Coli based product. It
has six phases inside of that product, so it's a
cocktail of phases and the majority of those phases are
engineered to carry the entire crisper castori construct inside.
Speaker 1 (10:09):
So it's basically six different phases, each of which you've
engineered to put on this gene shredder gene pac man.
So the ideas the phases go into the infecting cells,
the E coalie the bacteria, and then the Crisper eats
up the DNA of those bacteria, thus killing the bacteria.
That's the basic idea.
Speaker 2 (10:29):
That's the basic idea.
Speaker 1 (10:30):
So basically the idea is if you do a a
bunch of different phases and b add to them something
like Crisper casts three that makes it extra deadly, then
you can clear the infection rather than just reducing.
Speaker 2 (10:44):
Correct.
Speaker 1 (10:45):
And so now you are running a clinical trial on
women with recurrent urinary tract infections? Is that right?
Speaker 2 (10:53):
Correct?
Speaker 1 (10:54):
So tell me about that trial, like, where is it,
what's happening, what's the you know, what's the outcome?
Speaker 2 (11:01):
Yeah. So we just does patient two hundred and twenty
nine yesterday. We've got probably two hundred and eighty eight
to maybe three hundred and eight patients that we're going
to dose. And the idea is that it would not
only deal with the acute infection that you're getting hit
(11:22):
with right now, but it actually either eliminates or dramatically
reduces the number of recurrent infections that you'll see in
the future.
Speaker 1 (11:32):
Yeah, So tell me about like recurrent UTI as a problem.
Speaker 2 (11:37):
Inside the United States alone, over ten million people get
recurrent infections, of which two million of that patient block
get multiple recurrences. Once you get into a pattern of
having multiple recurrences, it's very difficult to get rid of those.
Many patients evolve through decades into a state of colonization,
(12:00):
which just simply means that that bacteria embeds itself somewhere
in your body and reinfections occur. You know, maybe for
some a few times a year, but for many five
six times a year.
Speaker 1 (12:12):
And how are you delivering the face treatment?
Speaker 2 (12:14):
So we have an intraor ethral delivery into the bladder,
So we use a catheter, we avoid the bladder of
its content, and then we reverse flow the drug product
into the bladder, and in the process we also expand
the bladder to make sure that the bladder wall is coded,
and we hold the drug product there for about forty
(12:34):
to fifty minutes before the patient's void. Again, we do
that on the first day and the second day, and
then simultaneously we have an intravenious backdrop that really is
meant to try to get to the kidneys, and we
do that on day one, two, and three, So the
total time and duration is three days.
Speaker 1 (12:54):
So this is an intense treatment. This is like your
uti would have to be extremely bad to want to
do this.
Speaker 2 (13:02):
Frankly, you're in that two million patient population. And you know,
if you had think about it this way, if you
had a urinary track infection that was so bad that
you had to stay home from work for three or
four days until the antibiotics that you got called in
for you kicked in, and then you were still under
the weather for another six or seven days, and then
(13:23):
at the end of that period, within a month to
two months, you got another one, and those infections just
in fact, when we talk to urologists and we talked
to eurogynecologists, they say that this particular infection is the
one that they feel the worst about for their patients
over anything that they deal with, because there's nothing that
(13:45):
they can really do about them except for treat them
with antibiotics as the occurrences happen, and just keep giving
them antibiotics every time they happen.
Speaker 1 (13:55):
What are the risks? What are the risks associated with
the fish treatment?
Speaker 2 (14:00):
So we have not seen any crazy averse events, but
the amount of viral particles that we put it into
the body, some patients can get low grade fever, some
patients can get a little nauseous.
Speaker 1 (14:16):
You're giving people a virus, right.
Speaker 2 (14:18):
You're giving a lot of virus.
Speaker 1 (14:21):
So when are you going to know if phase plus
antibiotic works better than antibiotical one.
Speaker 2 (14:29):
So we should be finished dosing. We believe we'll be
finished dosing sometime in the late fall to early winter,
and then within ninety days from that last dose we'll
have the data.
Speaker 1 (14:42):
So next less than a year. You should know.
Speaker 2 (14:45):
Definitely less than a year.
Speaker 1 (14:47):
So this UTI study is the one that's farthest along
for you, what else do you have in clinical trials?
Speaker 2 (14:55):
So we have applied for an ID for a Crone's
asset to try to essentially have an oral product that
is similar to the UTI product but works more towards
adherent invasive equal LIE, which is in many areas of medicine,
(15:16):
considered to be at worst associative at best causal of
Crohn's disease. In addition to that one, we're very close
to being able to submit an I and D for
this hospital acquired pneumonia asset, and that should be if
we're on time, that one should get approved before the
(15:37):
end of the year. So in theory, by the end
of this year, in the beginning of next year, we
would have three to four assets that we're moving through
the clinic.
Speaker 1 (15:46):
And an asset is a drug. An asset's a drug,
a drug that you own. That's why it's an asset
for you.
Speaker 2 (15:51):
Well, in some cases partnered, but yes, one that we own.
Speaker 1 (15:55):
Or co own. Yeah, somebody owns. We'll be back in
just a minute. Tell me about how you're using AI
(16:17):
at your company.
Speaker 2 (16:18):
Yeah, so we use a what we call AI driven robotics,
and so we discover phase at a volume I don't
think anybody in the past has used. And then when
we get those phage isolated, we sequence them, we run
full characterization on them, and then we start running them
(16:38):
through prediction engines that help us figure out what payloads
to put into their genomes and which ones of those
should go together and do a fixed drug.
Speaker 1 (16:48):
So, so let me just take a sec to understand
that the prediction engines part, that second part that sounds
like AI. But what's the robot part and how is
it different than you know, what happens in a normal lab.
Speaker 2 (17:01):
Well, in a normal lab, you have a pipette, yeah
kind of, Yeah, you have a little thumb thing that
like depress and yeah, so you know discovering phases using
sort of your regular old run of the mill.
Speaker 1 (17:16):
So what what So, okay, what are you doing.
Speaker 2 (17:19):
We're using hundreds, if not thousands, of ninety six well
plates with the robot running twenty four hours a day,
essentially looking at wastewater that we pull from all fifty
states outside of international airports.
Speaker 1 (17:36):
Oh, you're doing outside of international airports because it's a
more biodiverse sample, Like hundred percentages are flying in from
all over the world in people's bodies in your samp
Like that. I love that.
Speaker 2 (17:48):
Yeah, that's really cool.
Speaker 1 (17:49):
Would you say wastewater like you just go to like
the sewer, Like, how do you actually do this?
Speaker 2 (17:54):
You reach out to the municipalities and you set up
opportunities to pull them. And I mean in the early
early days, we would go out there and we'd knock
on the door and we'd askay can we do this?
And in a lot of case as you can.
Speaker 1 (18:10):
And what's the order of magnitude of like how many
different phases your your system is going through?
Speaker 2 (18:17):
So we have found it probably eighty five hundred uniquely identified,
fully characterized phases against ninety nine different bacterial targets. So
less size and scale that most academic labs, if not
any academic lab could ever match.
Speaker 1 (18:35):
So then so that's that's the robot stage. And then
you were saying, you move on to the to the
kind of AI stage. What's that?
Speaker 2 (18:43):
So you maybe the best way to think about is
it can work a little bit like Netflix. So if
your you know, you watch a particular type of movie
and there's a little algorithm behind the scenes that tries
to figure out, well, what's the next best movie that's
like that that you might want. And so we essentially
(19:04):
apply very similar models to the sequenced information that we
have on each of these unique phases, and we start
to try to figure out, really by evaluating quadrillions of
different options of pairing hundreds of not thousands of phase together,
which one which four or five, six or seven of
these go best together?
Speaker 1 (19:24):
So you want them to be complementary. You're targeting you're
targeting some particular bacteria, and you're like, okay, give me
the best cocktail correct AI.
Speaker 2 (19:33):
Yep. And then once it says try these top three,
we go make them and then we grow it up
and you know, manufacture small quantities of it, and then
we test them out.
Speaker 1 (19:43):
And is that how you got the cocktails that are
in trials now.
Speaker 2 (19:46):
The one that we have that's in trial now probably
was a bit more manual because it's our first asset
and it's probably built like seven years ago. The two,
the three that we have that are coming this year,
we're all built using that approach. So we're excited about
the second generation assets that are going in.
Speaker 1 (20:08):
So so let's talk more long term, Like, let's talk
about the sort of phase dream I've heard you talk about,
you know, the potential that the kinds of things you're
working on might go beyond what we think of as
infectious disease someday. Tell me about the sort of big,
big dream for phase treatment.
Speaker 2 (20:28):
I think crones sits in that arena for us. So
Crone's disease is a immune disorder that essentially your body's
immune system mistakes something in your intestinal track for an infection,
and it targets your own intestinal organs and eats away
(20:49):
at them to the point where you have small lesions
that are actually in your intestinal lining. And what we
know how to do in the field of medicine is
essentially turned down the intensity of the attacking.
Speaker 1 (21:05):
So it's an autoimmune disorder. It's not thought of as
infectious disease. Correct, So where does where does face therapy
come in?
Speaker 2 (21:15):
In many circles of ib D, it's thought that bacteria
is what the immune system is attacking.
Speaker 1 (21:23):
And IBD is inflammatory bowel disease. It's like that crones
is one of.
Speaker 2 (21:27):
Your crones colitis variant forms of those anything that essentially
diverticulated these types of things consider essentially intestinal organ disorders.
There's a big umbrella term for IBD. And so many
scientists believe that there are bacteria that gets stuck in
(21:48):
there and are non transient, and it's those bacteria that
get stuck in there and somehow adhere to the intestinal walls,
that that is what the immune system is attacking.
Speaker 1 (22:01):
And that makes your immune system freak out and start
attacking not just those cells but the bodies own cells.
Speaker 2 (22:07):
Correct. And so are drugs. And what we think is
the holy grail of medicine is to be able to
use phage encoded with payloads that can eat through either
the biofilms, mucle layers or macrophage layers that protect those
intracellular pathogens that our drugs would be able to get
there precisely and kill just those pathogens, thereby causing the
(22:33):
immune system to calm down and to potentially heal that
patient with something that's curative.
Speaker 1 (22:41):
And just to be clear, is it the case that
antibiotics just don't work for the particular the bacteria in
the setting that you're describing.
Speaker 2 (22:50):
Antibiotics are known to not be able to kill intracellular pathogens.
They can't transit into the human cells to kill the human.
Speaker 1 (22:58):
Cells, which is why they don't kill us.
Speaker 2 (23:01):
Presumably why antibiotics don't kill us. Yeah, presumably, I mean,
that's one way to look at it.
Speaker 1 (23:08):
Absolutely, yeah, Yeah, And this is a trial that you're
hoping you're hoping to sort of start a clinical trial
based on this hypothesis. You said in the next year
or so, we hope.
Speaker 2 (23:19):
To, We hope to. We still need to raise fund
specifically for that one.
Speaker 1 (23:23):
I believe it less the way you say we hope to.
Speaker 2 (23:26):
Yeah, that when you're running a company like this, you
tend to go where your contracts and partnerships are, and
right now we have contracts in three of four areas,
and so of course we're busy working on all three
of those, and we hope to add the fourth.
Speaker 1 (23:41):
So what's the bigger idea here? Like, we kind of
went far into the weeds on crumbs, But what is
the bigger idea for you know, if you're right, like,
what is the big hope for phaci therapy and whatever
ten years or something.
Speaker 2 (23:53):
So I'll start high level and go down into that.
Inflammation in the human body is not good. It causes
many diseases without question, things like rumtory torte is potentially
neuro disease is Things related to dementia, Parkinson's, etc. Like
when inflammation occurs in certain sections of the body, bad
(24:16):
things happen. Our hope for this platform is that it
can reach into the human body via precision medicine and
pull those pathogens or pathobians out.
Speaker 1 (24:28):
Is the underlying hypothesis that this sort of mysterious systemic
inflammation is caused by particular kinds of bacterial infection.
Speaker 2 (24:36):
Yes, many pathogens that are in the body are bad actors.
They're non transient, and the immune system is likely attacking
those non transient bad actors. And so if you have
a platform that can remove those bad actors, you likely
also get the benefits of being able to improve the
(24:57):
health of the human body, and that we believe will
do things like increase the lives of most people in society.
Or if you're genetically predisposed to a disease, you may
be able to prevent the onset of that disease for
a longer period of time. If you're genetically predisposed to
a disease, you might be able to lessen the severity
(25:20):
of that disease on your life. A good example might
be rheumatory authritis. So if you remove pathogens that either
aggravate or cause rhumatory authritis, can you help that patient
with their symptomology. Can you decrease the pain that's associated
in your joints with that disease by decreasing the amount
(25:41):
of pathogens that you actually have in the body. We
believe that that is a theory that is absolutely worth
going after trying to figure out. And many people don't
really realize this, but a lot of medicine is built
on suppression. GOLP wants, autoimmune drugs. These things are basically
(26:05):
shutting something down in the body to help a patient.
They're not actually dealing with causes, and so hopefully also
then we can start to talk about cures. But certainly
if we're able to show direct causal relationships between certain
(26:26):
pathogens that are in the body and improvement and disease symptomology,
I think we're onto something really, really big.
Speaker 1 (26:37):
We'll be back in a minute with the liking round.
What's your favorite phase?
Speaker 2 (26:51):
My favorite PHASEE?
Speaker 1 (26:53):
Yeah?
Speaker 2 (26:55):
Actually I really enjoy thinking about macrophages.
Speaker 1 (26:59):
Oh, the giant ones that they didn't even know where
virus is because they're so big.
Speaker 2 (27:03):
Yeah, they tend to evolve really fast and move around
on you, so it makes it a little bit interesting
to figure out out how to actually pin one down
and keep it from doing that when you don't want
it to. But the possibilities of what you can load
into a phase, the size of the payload that you
could get in there, if you could replicate it, that's
pretty exciting.
Speaker 1 (27:23):
So as a phase engineer, you're like, if we could
tame that guy, we could stick anything in there.
Speaker 2 (27:27):
Yeah, I guess it'd be like taming a really big bull, right,
Like what we get from that? I think the idea
of being able to put all kinds of different peptides
or other enzmatic tools into a phaseI and getting it
very specifically into a certain part of the body and
then having it in c too manufacture that payload right
(27:47):
at the site where you want it. It's pretty fascinating
as someone who's been in the industry for a number
of decades. There's tons of good drugs that are on
the shelf because of things like half life considerations, where
it just doesn't stay alive and active long enough.
Speaker 1 (28:03):
Huh.
Speaker 2 (28:04):
But if you're manufacturing it in the body right where
you need it with a phage, what can you do
with those peptides that have long since been on the shelf.
So I think there's some really cool things you can
do with phases that are larger that might be able
to carry some cool stuff.
Speaker 1 (28:21):
I heard you say that part of the reason you
started a company was because you don't have a PhD.
And you realize that in bigger companies there was just
a ceiling on what you could do without a PhD.
And I'm curious, have you found any advantages of not
having a PhD. Does it give you any kind of
a inside or edge that you might not have if
(28:42):
you did have one.
Speaker 2 (28:43):
I mean, you can ask dumber questions of your team
and get away with it. It sort of like why
do you think that I don't understand? Explain that to me.
Speaker 1 (28:52):
That's actually I will say, that's my whole game. That's
like my job is. It's like I don't understand that.
Explained it to me.
Speaker 2 (28:58):
I also think that it gives us. It gives our
culture inside of our company a bias towards more execution.
And not that we're any less curious about scientific discovery,
but once you pass a certain point where you're moving
into the clinic and through the clinic, it's time to execute,
and so you stay focused a little bit better.
Speaker 1 (29:19):
Right. You're an engineer by training, right, that's a very
engineering mindset. Right, let's build a thing.
Speaker 2 (29:25):
Yeah, I'm a project manager by background. I'm a project manager.
That's what I was. I guess raised doing is running
huge projects.
Speaker 1 (29:34):
So you've been in biotech for what thirty more than
thirty years, right, which is ye a long time. And
I'm curious if you sort of look over the arc,
if you go back to when you were starting, I'm
curious what's surprising to you, Like, what has done better
than you expected? What has done worse?
Speaker 2 (29:54):
That's a really no one's ever asked me that one before. Okay,
I mean, I think on the better side, I really
have been in awe and excited about cures I started.
If you said, hey, we're working on a cure, people
would look at you and you'd immediately be discredited.
Speaker 1 (30:17):
So what can we cure now that we couldn't cure
when you started?
Speaker 2 (30:20):
I don't think you necessarily have all of the cures
for things like do Chanes or Parkinson's or Alzheimer's that.
Speaker 1 (30:28):
Are definitely not for those, But what can we cure?
Speaker 2 (30:32):
I think they're I think they're coming. And that's that's
my answer to your question of what's really cool about
biotech the hard parts, the parts that maybe aren't so
fun is I think we had just a huge bullet
of garbage ideas that flooded into the industry post COVID.
The amount of money that came into the industry post COVID,
(30:54):
the craze around SPACs. It basically drained all the talent
into a bunch of BS companies, and it took a
couple of years for that to flood out.
Speaker 1 (31:03):
The curse of too much money. It's funny people mention
that more often than I would have thought.
Speaker 2 (31:09):
In an industry that's used to creating four hundred companies
per year. You don't want to create four thousand for two.
And that's not you just don't have the talent enough
in the executive and leadership ranks to hold that. And
where you get that from as your service partners, you're
your vendors, and then your vendors don't know what they're doing.
(31:30):
And so we had to live through that. I think
we're through that. I actually think we're on the other
side of that, which is I guess time will tell
as we see what actually breaks through.
Speaker 1 (31:46):
Paul Gariffolo is the co founder and CEO of Locust Biosciences.
Please let us know what you think of the show.
Do you want to hear more of, which you want
to hear less of? Would you go guest ideas? You
can email us at problem at pushkin dot fm. I
read all the emails. You can also find me on
x LinkedIn. Do appreciate all the messages that we get.
(32:12):
Today's show was produced by Gabriel Hunter Chang and Trina Menino.
It was engineered by Hans Dale She and edited by
Lydia Jean Kott. I'm Jacob Goldstein and we'll be back
next week with another episode of What's Your Problem,
Popular Podcasts
Betrayal Weekly
Betrayal Weekly is back for a new season. Every Thursday, Betrayal Weekly shares first-hand accounts of broken trust, shocking deceptions, and the trail of destruction they leave behind. Hosted by Andrea Gunning, this weekly ongoing series digs into real-life stories of betrayal and the aftermath. From stories of double lives to dark discoveries, these are cautionary tales and accounts of resilience against all odds. From the producers of the critically acclaimed Betrayal series, Betrayal Weekly drops new episodes every Thursday. If you would like to share your story, you can reach out to the Betrayal Team by emailing them at betrayalpod@gmail.com and follow us on Instagram at @betrayalpod and @glasspodcasts. Please join our Substack for additional exclusive content, curated book recommendations, and community discussions. Sign up FREE by clicking this link Beyond Betrayal Substack. Join our community dedicated to truth, resilience, and healing. Your voice matters! Be a part of our Betrayal journey on Substack.
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Dateline NBC
Current and classic episodes, featuring compelling true-crime mysteries, powerful documentaries and in-depth investigations. Follow now to get the latest episodes of Dateline NBC completely free, or subscribe to Dateline Premium for ad-free listening and exclusive bonus content: DatelinePremium.com