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Speaker 1: Pushkin. I love phages. Phages are viruses that attack bacteria.

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Speaker 1: Phages are unimaginably abundant, a trillion phages for every grain

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Speaker 1: of sand on Earth, according to one estimate, which what

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Speaker 1: does that even mean? Qualitatively? It means phages are all

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Speaker 1: around us, they are inside of us, They're essential to

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Speaker 1: life on earth, and they may help to improve human

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Speaker 1: health in a profound way. I'm Jacob Goldstein. This is

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Speaker 1: what's your problem? And my guest today is Paul Garifolo.

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Speaker 1: He is the co founder and CEO of a company

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Speaker 1: called Locust Biosciences. Paul's problem is this, can you use

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Speaker 1: genetically engineered phages to cure disease? People have been trying

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Speaker 1: to use phages to cure infections for over one hundred

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Speaker 1: years now, but in most cases, naturally occurring phages just

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Speaker 1: don't work as well as antibiotics as drugs. Phages reduce infections,

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Speaker 1: but they often don't wipe them out entirely. So Paul

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Speaker 1: and his colleagues are taking a different approach. They're genetically

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Speaker 1: engineering phages to make them better at killing bacteria. For now,

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Speaker 1: the company is testing its first phage based drug in

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Speaker 1: patients in combination with antibiotics. But Paul says, the long

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Speaker 1: term dream is bigger than that.

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Speaker 2: So we actually have been trying to figure out how

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Speaker 2: to selectively remove bacteria from the human body without touching

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Speaker 2: any of the good bacteria that's in there, and we

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Speaker 2: believe that that is a key to longevity of human life.

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Speaker 2: We're starting with trying to replace antibiotics, but we believe

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Speaker 2: that any number of diseases in the human body or

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Speaker 2: actually the body's reaction to inflammation from bad bacteria getting

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Speaker 2: in there and not leaving. And so that's what Locus

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Speaker 2: is trying to do.

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Speaker 1: That's the big dream. There's a narrower dream that I'm

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Speaker 1: also interested in, yes, and that maybe a question that

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Speaker 1: gets at the narrow dream is what are the limitations

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Speaker 1: of antibiotics that you're trying to address.

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Speaker 2: I think there are two things that are wrong with antibiotics.

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Speaker 2: So one that most people are very, very familiar with

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Speaker 2: is resistance is now everywhere, and so effectively we're beginning

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Speaker 2: to see exponential increases in drug resists from almost all

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Speaker 2: mainstream antibiotics, if not all. So there's sort of a

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Speaker 2: math problem from here. At some point none of them

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Speaker 2: work and the further up in strength you move in antibiotics,

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Speaker 2: the more toxic they are to your body. And so

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Speaker 2: if you're really sick and you have to go on

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Speaker 2: a really strong antibiotic, the antibiotic itself can be your demise.

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Speaker 2: So that's one thing. Another example might be people with

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Speaker 2: recurrent ear infections or recurrent bladder infections end up going

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Speaker 2: onto frequent batteries of antibiotics, say, you know, starting at

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Speaker 2: fifteen days, but eventually getting the things like thirty days

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Speaker 2: or forty five days of low volumes, and that can

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Speaker 2: wreak havoc on your body. You know, it could basically

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Speaker 2: destroy the balance in your microbiome. And you can have

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Speaker 2: things that are long ranging side, like having to go

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Speaker 2: on substantially simplistic diets for a long period of time

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Speaker 2: because your intestinal track can't handle the variety of food

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Speaker 2: that it likely needs for longevity. So those are just

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Speaker 2: a couple of examples.

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Speaker 1: Why my phages help to solve this problem.

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Speaker 2: So we think that phases are one of the most

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Speaker 2: unique and creative ways of getting into the human body

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Speaker 2: to selectively attack a very specific bacterial pathogen or pathobian

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Speaker 2: of interest, and only that particular target so I'm sure

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Speaker 2: you've heard about precision medicine on the gene editing side

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Speaker 2: for human cells that might be able to fix some

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Speaker 2: of the world's roughest diseases. But on the bacterial side,

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Speaker 2: precision medicine is quite new, And the idea of using

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Speaker 2: phases as a delivery vector is essentially centering around the

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Speaker 2: fact that they're exquisitely unique to the bacteria that they've

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Speaker 2: evolved to infect. And so I think the largest, most

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Speaker 2: abundant and oldest biological organism on the planet besides bacteria

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Speaker 2: is faish.

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Speaker 1: Yeah, that's amazing, right, Like the Earth is full of

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Speaker 1: phases in the sea. When every day half of the

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Speaker 1: bacteria and the sea get killed by stages or something like,

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Speaker 1: it's wild, right, It's like it's incredible.

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Speaker 2: Yeah, they say that half the bacteria on the planet,

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Speaker 2: soil sea in Europe.

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Speaker 1: Every day, Like it's happening all around us. It's happening

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Speaker 1: inside our bodies, right, there are phases that naturally occur

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Speaker 1: inside our.

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Speaker 2: Bodies, and bacteria actually double at a very similar pace, right,

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Speaker 2: So that this is one of nature's oldest and most

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Speaker 2: established ecosystems.

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Speaker 1: And this is an old idea it's super exciting when

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Speaker 1: you hear it and they're like, oh wait, people have

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Speaker 1: been trying to attack bacterial infection with phages for literally

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Speaker 1: like one hundred years, right, and I haven't got that

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Speaker 1: far with it. It sounds perfect. Why hasn't it worked

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Speaker 1: that well so far?

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Speaker 2: I think there are probably two or three reasons of note.

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Speaker 2: One is that people essentially since i'd say a century

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Speaker 2: ago when they were discovered, they use wild type phases,

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Speaker 2: meaning they don't do any type of enhancement to that virus,

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Speaker 2: They don't change the genome in any way. They simply

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Speaker 2: search for one that is effectively a good killer in

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Speaker 2: an academic lab, and then they take that killer and

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Speaker 2: they put that into the human body expecting similar results.

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Speaker 2: And you can see efficacylevels of those types of what

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Speaker 2: we call wild type phase treatments in anywhere from fifty

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Speaker 2: to maybe even sixty five maybe even in best cases

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Speaker 2: seventy percent range, which you would say, well, that sounds decent,

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Speaker 2: pretty good, But antibiotics have traditionally, up until when resistance

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Speaker 2: has started to come into fray, those typically work around

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Speaker 2: or above ninety five percent. So the efficacy difference between

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Speaker 2: those two wild type phases and antibiotics is just so stark.

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Speaker 2: In the days of the Cold War, antibiotics were not

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Speaker 2: really available to people that were behind the Iron Curtain,

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Speaker 2: and so face there be actually continued in many places

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Speaker 2: inside Georgia, Russia, et cetera, and advanced into treatment centers

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Speaker 2: that really were gear around a single phage for a

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Speaker 2: single bacteria. And what that leads me to this sort

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Speaker 2: of the second I think not shortcoming, but just natural

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Speaker 2: component of phase, which is an individual PHASEE to go after.

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Speaker 2: Let's say, a large population of bacteria in the human

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Speaker 2: body will begin to see resistance.

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Speaker 1: So that's the story of as you said, wild type

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Speaker 1: phasi is naturally occurring phasis, you're doing something much more

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Speaker 1: twenty first century right in a few ways. So we

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Speaker 1: should introduce another sort of idea slash piece of jargon now, right,

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Speaker 1: which is crisper cast three. People are used to think

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Speaker 1: of crisper as like the gene scissors, right. I think

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Speaker 1: people are relatively familiar with that, But this is a

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Speaker 1: variant that is like the gene shredder, right, as opposed

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Speaker 1: to a scissors.

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Speaker 2: Yes, it works like essentially a pac Man if you

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Speaker 2: remember the old arcade game. So it essentially makes a

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Speaker 2: small nick in one strand of the DNA of the

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Speaker 2: double helix, and then it choose that strand back by hundreds,

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Speaker 2: if not thousands of base pairs to the point where

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Speaker 2: it renders that that cell dead and by no means.

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Speaker 2: And I think this is an evolution of our company

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Speaker 2: and perhaps many others. Chrisper systems are not the only

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Speaker 2: thing that you can engineer into a phage, Peptides, other enzymes,

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Speaker 2: all kinds of things.

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Speaker 1: Oh interesting, but that's I mean, just to be clear,

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Speaker 1: Like the I call them drugs, they're drugs, rightugs. The

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Speaker 1: drugs that you have in clinical trials are combining crisper

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Speaker 1: cast three with a phage, right, Yes.

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Speaker 2: Our lead asset is an E. Coli based product. It

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Speaker 2: has six phases inside of that product, so it's a

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Speaker 2: cocktail of phases and the majority of those phases are

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Speaker 2: engineered to carry the entire crisper castori construct inside.

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Speaker 1: So it's basically six different phases, each of which you've

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Speaker 1: engineered to put on this gene shredder gene pac man.

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Speaker 1: So the ideas the phases go into the infecting cells,

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Speaker 1: the E coalie the bacteria, and then the Crisper eats

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Speaker 1: up the DNA of those bacteria, thus killing the bacteria.

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Speaker 1: That's the basic idea.

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Speaker 2: That's the basic idea.

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Speaker 1: So basically the idea is if you do a a

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Speaker 1: bunch of different phases and b add to them something

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Speaker 1: like Crisper casts three that makes it extra deadly, then

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Speaker 1: you can clear the infection rather than just reducing.

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Speaker 2: Correct.

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Speaker 1: And so now you are running a clinical trial on

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Speaker 1: women with recurrent urinary tract infections? Is that right?

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Speaker 2: Correct?

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Speaker 1: So tell me about that trial, like, where is it,

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Speaker 1: what's happening, what's the you know, what's the outcome?

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Speaker 2: Yeah. So we just does patient two hundred and twenty

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Speaker 2: nine yesterday. We've got probably two hundred and eighty eight

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Speaker 2: to maybe three hundred and eight patients that we're going

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Speaker 2: to dose. And the idea is that it would not

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Speaker 2: only deal with the acute infection that you're getting hit

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Speaker 2: with right now, but it actually either eliminates or dramatically

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Speaker 2: reduces the number of recurrent infections that you'll see in

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Speaker 2: the future.

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Speaker 1: Yeah, So tell me about like recurrent UTI as a problem.

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Speaker 2: Inside the United States alone, over ten million people get

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Speaker 2: recurrent infections, of which two million of that patient block

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Speaker 2: get multiple recurrences. Once you get into a pattern of

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Speaker 2: having multiple recurrences, it's very difficult to get rid of those.

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Speaker 2: Many patients evolve through decades into a state of colonization,

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Speaker 2: which just simply means that that bacteria embeds itself somewhere

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Speaker 2: in your body and reinfections occur. You know, maybe for

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Speaker 2: some a few times a year, but for many five

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Speaker 2: six times a year.

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Speaker 1: And how are you delivering the face treatment?

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Speaker 2: So we have an intraor ethral delivery into the bladder,

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Speaker 2: So we use a catheter, we avoid the bladder of

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Speaker 2: its content, and then we reverse flow the drug product

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Speaker 2: into the bladder, and in the process we also expand

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Speaker 2: the bladder to make sure that the bladder wall is coded,

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Speaker 2: and we hold the drug product there for about forty

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Speaker 2: to fifty minutes before the patient's void. Again, we do

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Speaker 2: that on the first day and the second day, and

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Speaker 2: then simultaneously we have an intravenious backdrop that really is

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Speaker 2: meant to try to get to the kidneys, and we

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Speaker 2: do that on day one, two, and three, So the

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Speaker 2: total time and duration is three days.

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Speaker 1: So this is an intense treatment. This is like your

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Speaker 1: uti would have to be extremely bad to want to

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Speaker 1: do this.

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Speaker 2: Frankly, you're in that two million patient population. And you know,

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Speaker 2: if you had think about it this way, if you

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Speaker 2: had a urinary track infection that was so bad that

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Speaker 2: you had to stay home from work for three or

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Speaker 2: four days until the antibiotics that you got called in

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Speaker 2: for you kicked in, and then you were still under

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Speaker 2: the weather for another six or seven days, and then

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Speaker 2: at the end of that period, within a month to

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Speaker 2: two months, you got another one, and those infections just

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Speaker 2: in fact, when we talk to urologists and we talked

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Speaker 2: to eurogynecologists, they say that this particular infection is the

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Speaker 2: one that they feel the worst about for their patients

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Speaker 2: over anything that they deal with, because there's nothing that

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Speaker 2: they can really do about them except for treat them

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Speaker 2: with antibiotics as the occurrences happen, and just keep giving

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Speaker 2: them antibiotics every time they happen.

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Speaker 1: What are the risks? What are the risks associated with

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Speaker 1: the fish treatment?

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Speaker 2: So we have not seen any crazy averse events, but

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Speaker 2: the amount of viral particles that we put it into

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Speaker 2: the body, some patients can get low grade fever, some

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Speaker 2: patients can get a little nauseous.

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Speaker 1: You're giving people a virus, right.

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Speaker 2: You're giving a lot of virus.

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Speaker 1: So when are you going to know if phase plus

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Speaker 1: antibiotic works better than antibiotical one.

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Speaker 2: So we should be finished dosing. We believe we'll be

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Speaker 2: finished dosing sometime in the late fall to early winter,

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Speaker 2: and then within ninety days from that last dose we'll

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Speaker 2: have the data.

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Speaker 1: So next less than a year. You should know.

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Speaker 2: Definitely less than a year.

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Speaker 1: So this UTI study is the one that's farthest along

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Speaker 1: for you, what else do you have in clinical trials?

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Speaker 2: So we have applied for an ID for a Crone's

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Speaker 2: asset to try to essentially have an oral product that

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Speaker 2: is similar to the UTI product but works more towards

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Speaker 2: adherent invasive equal LIE, which is in many areas of medicine,

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Speaker 2: considered to be at worst associative at best causal of

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Speaker 2: Crohn's disease. In addition to that one, we're very close

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Speaker 2: to being able to submit an I and D for

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Speaker 2: this hospital acquired pneumonia asset, and that should be if

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Speaker 2: we're on time, that one should get approved before the

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Speaker 2: end of the year. So in theory, by the end

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Speaker 2: of this year, in the beginning of next year, we

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Speaker 2: would have three to four assets that we're moving through

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Speaker 2: the clinic.

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Speaker 1: And an asset is a drug. An asset's a drug,

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Speaker 1: a drug that you own. That's why it's an asset

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Speaker 1: for you.

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Speaker 2: Well, in some cases partnered, but yes, one that we own.

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Speaker 1: Or co own. Yeah, somebody owns. We'll be back in

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Speaker 1: just a minute. Tell me about how you're using AI

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Speaker 1: at your company.

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Speaker 2: Yeah, so we use a what we call AI driven robotics,

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Speaker 2: and so we discover phase at a volume I don't

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Speaker 2: think anybody in the past has used. And then when

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Speaker 2: we get those phage isolated, we sequence them, we run

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Speaker 2: full characterization on them, and then we start running them

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Speaker 2: through prediction engines that help us figure out what payloads

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Speaker 2: to put into their genomes and which ones of those

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Speaker 2: should go together and do a fixed drug.

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Speaker 1: So, so let me just take a sec to understand

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Speaker 1: that the prediction engines part, that second part that sounds

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Speaker 1: like AI. But what's the robot part and how is

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Speaker 1: it different than you know, what happens in a normal lab.

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Speaker 2: Well, in a normal lab, you have a pipette, yeah

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Speaker 2: kind of, Yeah, you have a little thumb thing that

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Speaker 2: like depress and yeah, so you know discovering phases using

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Speaker 2: sort of your regular old run of the mill.

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Speaker 1: So what what So, okay, what are you doing.

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Speaker 2: We're using hundreds, if not thousands, of ninety six well

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Speaker 2: plates with the robot running twenty four hours a day,

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Speaker 2: essentially looking at wastewater that we pull from all fifty

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Speaker 2: states outside of international airports.

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Speaker 1: Oh, you're doing outside of international airports because it's a

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Speaker 1: more biodiverse sample, Like hundred percentages are flying in from

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Speaker 1: all over the world in people's bodies in your samp

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Speaker 1: Like that. I love that.

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Speaker 2: Yeah, that's really cool.

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Speaker 1: Would you say wastewater like you just go to like

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Speaker 1: the sewer, Like, how do you actually do this?

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Speaker 2: You reach out to the municipalities and you set up

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Speaker 2: opportunities to pull them. And I mean in the early

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Speaker 2: early days, we would go out there and we'd knock

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Speaker 2: on the door and we'd askay can we do this?

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Speaker 2: And in a lot of case as you can.

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Speaker 1: And what's the order of magnitude of like how many

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Speaker 1: different phases your your system is going through?

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Speaker 2: So we have found it probably eighty five hundred uniquely identified,

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Speaker 2: fully characterized phases against ninety nine different bacterial targets. So

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Speaker 2: less size and scale that most academic labs, if not

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Speaker 2: any academic lab could ever match.

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Speaker 1: So then so that's that's the robot stage. And then

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Speaker 1: you were saying, you move on to the to the

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Speaker 1: kind of AI stage. What's that?

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Speaker 2: So you maybe the best way to think about is

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Speaker 2: it can work a little bit like Netflix. So if

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Speaker 2: your you know, you watch a particular type of movie

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Speaker 2: and there's a little algorithm behind the scenes that tries

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Speaker 2: to figure out, well, what's the next best movie that's

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Speaker 2: like that that you might want. And so we essentially

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Speaker 2: apply very similar models to the sequenced information that we

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Speaker 2: have on each of these unique phases, and we start

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Speaker 2: to try to figure out, really by evaluating quadrillions of

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Speaker 2: different options of pairing hundreds of not thousands of phase together,

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Speaker 2: which one which four or five, six or seven of

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Speaker 2: these go best together?

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Speaker 1: So you want them to be complementary. You're targeting you're

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Speaker 1: targeting some particular bacteria, and you're like, okay, give me

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Speaker 1: the best cocktail correct AI.

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Speaker 2: Yep. And then once it says try these top three,

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Speaker 2: we go make them and then we grow it up

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Speaker 2: and you know, manufacture small quantities of it, and then

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Speaker 2: we test them out.

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Speaker 1: And is that how you got the cocktails that are

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Speaker 1: in trials now.

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Speaker 2: The one that we have that's in trial now probably

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Speaker 2: was a bit more manual because it's our first asset

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Speaker 2: and it's probably built like seven years ago. The two,

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Speaker 2: the three that we have that are coming this year,

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Speaker 2: we're all built using that approach. So we're excited about

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Speaker 2: the second generation assets that are going in.

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Speaker 1: So so let's talk more long term, Like, let's talk

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Speaker 1: about the sort of phase dream I've heard you talk about,

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Speaker 1: you know, the potential that the kinds of things you're

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Speaker 1: working on might go beyond what we think of as

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Speaker 1: infectious disease someday. Tell me about the sort of big,

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Speaker 1: big dream for phase treatment.

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Speaker 2: I think crones sits in that arena for us. So

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Speaker 2: Crone's disease is a immune disorder that essentially your body's

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Speaker 2: immune system mistakes something in your intestinal track for an infection,

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Speaker 2: and it targets your own intestinal organs and eats away

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Speaker 2: at them to the point where you have small lesions

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Speaker 2: that are actually in your intestinal lining. And what we

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Speaker 2: know how to do in the field of medicine is

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Speaker 2: essentially turned down the intensity of the attacking.

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Speaker 1: So it's an autoimmune disorder. It's not thought of as

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Speaker 1: infectious disease. Correct, So where does where does face therapy

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Speaker 1: come in?

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Speaker 2: In many circles of ib D, it's thought that bacteria

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Speaker 2: is what the immune system is attacking.

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Speaker 1: And IBD is inflammatory bowel disease. It's like that crones

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Speaker 1: is one of.

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Speaker 2: Your crones colitis variant forms of those anything that essentially

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Speaker 2: diverticulated these types of things consider essentially intestinal organ disorders.

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Speaker 2: There's a big umbrella term for IBD. And so many

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Speaker 2: scientists believe that there are bacteria that gets stuck in

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Speaker 2: there and are non transient, and it's those bacteria that

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Speaker 2: get stuck in there and somehow adhere to the intestinal walls,

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Speaker 2: that that is what the immune system is attacking.

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Speaker 1: And that makes your immune system freak out and start

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Speaker 1: attacking not just those cells but the bodies own cells.

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Speaker 2: Correct. And so are drugs. And what we think is

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Speaker 2: the holy grail of medicine is to be able to

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Speaker 2: use phage encoded with payloads that can eat through either

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Speaker 2: the biofilms, mucle layers or macrophage layers that protect those

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Speaker 2: intracellular pathogens that our drugs would be able to get

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Speaker 2: there precisely and kill just those pathogens, thereby causing the

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Speaker 2: immune system to calm down and to potentially heal that

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Speaker 2: patient with something that's curative.

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Speaker 1: And just to be clear, is it the case that

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Speaker 1: antibiotics just don't work for the particular the bacteria in

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Speaker 1: the setting that you're describing.

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Speaker 2: Antibiotics are known to not be able to kill intracellular pathogens.

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Speaker 2: They can't transit into the human cells to kill the human.

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Speaker 1: Cells, which is why they don't kill us.

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Speaker 2: Presumably why antibiotics don't kill us. Yeah, presumably, I mean,

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Speaker 2: that's one way to look at it.

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Speaker 1: Absolutely, yeah, Yeah, And this is a trial that you're

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Speaker 1: hoping you're hoping to sort of start a clinical trial

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Speaker 1: based on this hypothesis. You said in the next year

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Speaker 1: or so, we hope.

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Speaker 2: To, We hope to. We still need to raise fund

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Speaker 2: specifically for that one.

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Speaker 1: I believe it less the way you say we hope to.

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Speaker 2: Yeah, that when you're running a company like this, you

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Speaker 2: tend to go where your contracts and partnerships are, and

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Speaker 2: right now we have contracts in three of four areas,

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Speaker 2: and so of course we're busy working on all three

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Speaker 2: of those, and we hope to add the fourth.

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Speaker 1: So what's the bigger idea here? Like, we kind of

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Speaker 1: went far into the weeds on crumbs, But what is

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Speaker 1: the bigger idea for you know, if you're right, like,

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Speaker 1: what is the big hope for phaci therapy and whatever

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Speaker 1: ten years or something.

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Speaker 2: So I'll start high level and go down into that.

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Speaker 2: Inflammation in the human body is not good. It causes

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Speaker 2: many diseases without question, things like rumtory torte is potentially

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Speaker 2: neuro disease is Things related to dementia, Parkinson's, etc. Like

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Speaker 2: when inflammation occurs in certain sections of the body, bad

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Speaker 2: things happen. Our hope for this platform is that it

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Speaker 2: can reach into the human body via precision medicine and

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Speaker 2: pull those pathogens or pathobians out.

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Speaker 1: Is the underlying hypothesis that this sort of mysterious systemic

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Speaker 1: inflammation is caused by particular kinds of bacterial infection.

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Speaker 2: Yes, many pathogens that are in the body are bad actors.

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Speaker 2: They're non transient, and the immune system is likely attacking

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Speaker 2: those non transient bad actors. And so if you have

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Speaker 2: a platform that can remove those bad actors, you likely

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Speaker 2: also get the benefits of being able to improve the

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Speaker 2: health of the human body, and that we believe will

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Speaker 2: do things like increase the lives of most people in society.

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Speaker 2: Or if you're genetically predisposed to a disease, you may

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Speaker 2: be able to prevent the onset of that disease for

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Speaker 2: a longer period of time. If you're genetically predisposed to

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Speaker 2: a disease, you might be able to lessen the severity

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Speaker 2: of that disease on your life. A good example might

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Speaker 2: be rheumatory authritis. So if you remove pathogens that either

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Speaker 2: aggravate or cause rhumatory authritis, can you help that patient

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Speaker 2: with their symptomology. Can you decrease the pain that's associated

403
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Speaker 2: in your joints with that disease by decreasing the amount

404
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Speaker 2: of pathogens that you actually have in the body. We

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Speaker 2: believe that that is a theory that is absolutely worth

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Speaker 2: going after trying to figure out. And many people don't

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Speaker 2: really realize this, but a lot of medicine is built

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Speaker 2: on suppression. GOLP wants, autoimmune drugs. These things are basically

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Speaker 2: shutting something down in the body to help a patient.

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Speaker 2: They're not actually dealing with causes, and so hopefully also

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Speaker 2: then we can start to talk about cures. But certainly

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Speaker 2: if we're able to show direct causal relationships between certain

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Speaker 2: pathogens that are in the body and improvement and disease symptomology,

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Speaker 2: I think we're onto something really, really big.

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Speaker 1: We'll be back in a minute with the liking round.

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Speaker 1: What's your favorite phase?

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Speaker 2: My favorite PHASEE?

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Speaker 1: Yeah?

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Speaker 2: Actually I really enjoy thinking about macrophages.

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Speaker 1: Oh, the giant ones that they didn't even know where

421
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Speaker 1: virus is because they're so big.

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Speaker 2: Yeah, they tend to evolve really fast and move around

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Speaker 2: on you, so it makes it a little bit interesting

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Speaker 2: to figure out out how to actually pin one down

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Speaker 2: and keep it from doing that when you don't want

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Speaker 2: it to. But the possibilities of what you can load

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Speaker 2: into a phase, the size of the payload that you

428
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Speaker 2: could get in there, if you could replicate it, that's

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Speaker 2: pretty exciting.

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Speaker 1: So as a phase engineer, you're like, if we could

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Speaker 1: tame that guy, we could stick anything in there.

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Speaker 2: Yeah, I guess it'd be like taming a really big bull, right,

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Speaker 2: Like what we get from that? I think the idea

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Speaker 2: of being able to put all kinds of different peptides

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00:27:37,596 --> 00:27:41,036
Speaker 2: or other enzmatic tools into a phaseI and getting it

436
00:27:41,156 --> 00:27:43,716
Speaker 2: very specifically into a certain part of the body and

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00:27:43,756 --> 00:27:47,796
Speaker 2: then having it in c too manufacture that payload right

438
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Speaker 2: at the site where you want it. It's pretty fascinating

439
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Speaker 2: as someone who's been in the industry for a number

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Speaker 2: of decades. There's tons of good drugs that are on

441
00:27:57,596 --> 00:28:00,636
Speaker 2: the shelf because of things like half life considerations, where

442
00:28:00,676 --> 00:28:03,676
Speaker 2: it just doesn't stay alive and active long enough.

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Speaker 1: Huh.

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Speaker 2: But if you're manufacturing it in the body right where

445
00:28:06,916 --> 00:28:09,036
Speaker 2: you need it with a phage, what can you do

446
00:28:09,316 --> 00:28:12,476
Speaker 2: with those peptides that have long since been on the shelf.

447
00:28:12,916 --> 00:28:15,196
Speaker 2: So I think there's some really cool things you can

448
00:28:15,236 --> 00:28:18,676
Speaker 2: do with phases that are larger that might be able

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00:28:18,676 --> 00:28:19,956
Speaker 2: to carry some cool stuff.

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Speaker 1: I heard you say that part of the reason you

451
00:28:23,516 --> 00:28:26,556
Speaker 1: started a company was because you don't have a PhD.

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00:28:26,716 --> 00:28:28,836
Speaker 1: And you realize that in bigger companies there was just

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Speaker 1: a ceiling on what you could do without a PhD.

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Speaker 1: And I'm curious, have you found any advantages of not

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00:28:38,116 --> 00:28:40,036
Speaker 1: having a PhD. Does it give you any kind of

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00:28:40,116 --> 00:28:42,556
Speaker 1: a inside or edge that you might not have if

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00:28:42,556 --> 00:28:43,316
Speaker 1: you did have one.

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Speaker 2: I mean, you can ask dumber questions of your team

459
00:28:46,036 --> 00:28:48,276
Speaker 2: and get away with it. It sort of like why

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00:28:48,356 --> 00:28:51,516
Speaker 2: do you think that I don't understand? Explain that to me.

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Speaker 1: That's actually I will say, that's my whole game. That's

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00:28:55,236 --> 00:28:57,596
Speaker 1: like my job is. It's like I don't understand that.

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00:28:57,676 --> 00:28:58,396
Speaker 1: Explained it to me.

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Speaker 2: I also think that it gives us. It gives our

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00:29:02,076 --> 00:29:05,396
Speaker 2: culture inside of our company a bias towards more execution.

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Speaker 2: And not that we're any less curious about scientific discovery,

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00:29:10,956 --> 00:29:13,996
Speaker 2: but once you pass a certain point where you're moving

468
00:29:14,036 --> 00:29:16,756
Speaker 2: into the clinic and through the clinic, it's time to execute,

469
00:29:16,836 --> 00:29:19,076
Speaker 2: and so you stay focused a little bit better.

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Speaker 1: Right. You're an engineer by training, right, that's a very

471
00:29:22,316 --> 00:29:24,876
Speaker 1: engineering mindset. Right, let's build a thing.

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00:29:25,116 --> 00:29:28,356
Speaker 2: Yeah, I'm a project manager by background. I'm a project manager.

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Speaker 2: That's what I was. I guess raised doing is running

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00:29:31,516 --> 00:29:32,396
Speaker 2: huge projects.

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Speaker 1: So you've been in biotech for what thirty more than

476
00:29:37,716 --> 00:29:40,796
Speaker 1: thirty years, right, which is ye a long time. And

477
00:29:40,956 --> 00:29:43,716
Speaker 1: I'm curious if you sort of look over the arc,

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Speaker 1: if you go back to when you were starting, I'm

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Speaker 1: curious what's surprising to you, Like, what has done better

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Speaker 1: than you expected? What has done worse?

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Speaker 2: That's a really no one's ever asked me that one before. Okay,

482
00:29:58,916 --> 00:30:03,356
Speaker 2: I mean, I think on the better side, I really

483
00:30:03,516 --> 00:30:09,956
Speaker 2: have been in awe and excited about cures I started.

484
00:30:10,796 --> 00:30:13,916
Speaker 2: If you said, hey, we're working on a cure, people

485
00:30:13,956 --> 00:30:16,716
Speaker 2: would look at you and you'd immediately be discredited.

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Speaker 1: So what can we cure now that we couldn't cure

487
00:30:19,196 --> 00:30:19,836
Speaker 1: when you started?

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00:30:20,036 --> 00:30:23,716
Speaker 2: I don't think you necessarily have all of the cures

489
00:30:23,716 --> 00:30:28,756
Speaker 2: for things like do Chanes or Parkinson's or Alzheimer's that.

490
00:30:28,756 --> 00:30:32,276
Speaker 1: Are definitely not for those, But what can we cure?

491
00:30:32,396 --> 00:30:36,116
Speaker 2: I think they're I think they're coming. And that's that's

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00:30:36,156 --> 00:30:38,876
Speaker 2: my answer to your question of what's really cool about

493
00:30:38,876 --> 00:30:42,716
Speaker 2: biotech the hard parts, the parts that maybe aren't so

494
00:30:42,876 --> 00:30:46,556
Speaker 2: fun is I think we had just a huge bullet

495
00:30:46,716 --> 00:30:50,796
Speaker 2: of garbage ideas that flooded into the industry post COVID.

496
00:30:51,156 --> 00:30:54,356
Speaker 2: The amount of money that came into the industry post COVID,

497
00:30:54,476 --> 00:30:59,156
Speaker 2: the craze around SPACs. It basically drained all the talent

498
00:30:59,316 --> 00:31:01,836
Speaker 2: into a bunch of BS companies, and it took a

499
00:31:01,836 --> 00:31:03,876
Speaker 2: couple of years for that to flood out.

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00:31:03,916 --> 00:31:06,756
Speaker 1: The curse of too much money. It's funny people mention

501
00:31:06,876 --> 00:31:08,756
Speaker 1: that more often than I would have thought.

502
00:31:09,396 --> 00:31:12,276
Speaker 2: In an industry that's used to creating four hundred companies

503
00:31:12,316 --> 00:31:14,876
Speaker 2: per year. You don't want to create four thousand for two.

504
00:31:15,556 --> 00:31:20,556
Speaker 2: And that's not you just don't have the talent enough

505
00:31:20,596 --> 00:31:23,516
Speaker 2: in the executive and leadership ranks to hold that. And

506
00:31:23,556 --> 00:31:26,276
Speaker 2: where you get that from as your service partners, you're

507
00:31:26,396 --> 00:31:29,636
Speaker 2: your vendors, and then your vendors don't know what they're doing.

508
00:31:30,316 --> 00:31:32,876
Speaker 2: And so we had to live through that. I think

509
00:31:32,916 --> 00:31:34,916
Speaker 2: we're through that. I actually think we're on the other

510
00:31:34,956 --> 00:31:37,596
Speaker 2: side of that, which is I guess time will tell

511
00:31:37,636 --> 00:31:39,636
Speaker 2: as we see what actually breaks through.

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Speaker 1: Paul Gariffolo is the co founder and CEO of Locust Biosciences.

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Speaker 1: Please let us know what you think of the show.

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00:31:55,156 --> 00:31:56,396
Speaker 1: Do you want to hear more of, which you want

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00:31:56,436 --> 00:32:00,156
Speaker 1: to hear less of? Would you go guest ideas? You

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00:32:00,196 --> 00:32:03,436
Speaker 1: can email us at problem at pushkin dot fm. I

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00:32:03,476 --> 00:32:05,996
Speaker 1: read all the emails. You can also find me on

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00:32:06,756 --> 00:32:11,436
Speaker 1: x LinkedIn. Do appreciate all the messages that we get.

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Speaker 1: Today's show was produced by Gabriel Hunter Chang and Trina Menino.

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00:32:15,196 --> 00:32:17,956
Speaker 1: It was engineered by Hans Dale She and edited by

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00:32:18,036 --> 00:32:21,156
Speaker 1: Lydia Jean Kott. I'm Jacob Goldstein and we'll be back

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Speaker 1: next week with another episode of What's Your Problem,