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