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Using Viruses to Fight Disease · What's Your Problem?

0:15
Speaker 1: Pushkin. I love phages. Phages are viruses that attack bacteria.
0:25
Speaker 1: Phages are unimaginably abundant, a trillion phages for every grain
0:32
Speaker 1: of sand on Earth, according to one estimate, which what
0:36
Speaker 1: does that even mean? Qualitatively? It means phages are all
0:40
Speaker 1: around us, they are inside of us, They're essential to
0:44
Speaker 1: life on earth, and they may help to improve human
0:48
Speaker 1: health in a profound way. I'm Jacob Goldstein. This is
1:03
Speaker 1: what's your problem? And my guest today is Paul Garifolo.
1:07
Speaker 1: He is the co founder and CEO of a company
1:09
Speaker 1: called Locust Biosciences. Paul's problem is this, can you use
1:15
Speaker 1: genetically engineered phages to cure disease? People have been trying
1:20
Speaker 1: to use phages to cure infections for over one hundred
1:23
Speaker 1: years now, but in most cases, naturally occurring phages just
1:28
Speaker 1: don't work as well as antibiotics as drugs. Phages reduce infections,
1:33
Speaker 1: but they often don't wipe them out entirely. So Paul
1:37
Speaker 1: and his colleagues are taking a different approach. They're genetically
1:40
Speaker 1: engineering phages to make them better at killing bacteria. For now,
1:45
Speaker 1: the company is testing its first phage based drug in
1:49
Speaker 1: patients in combination with antibiotics. But Paul says, the long
1:54
Speaker 1: term dream is bigger than that.
1:56
Speaker 2: So we actually have been trying to figure out how
2:00
Speaker 2: to selectively remove bacteria from the human body without touching
2:07
Speaker 2: any of the good bacteria that's in there, and we
2:10
Speaker 2: believe that that is a key to longevity of human life.
2:16
Speaker 2: We're starting with trying to replace antibiotics, but we believe
2:21
Speaker 2: that any number of diseases in the human body or
2:25
Speaker 2: actually the body's reaction to inflammation from bad bacteria getting
2:31
Speaker 2: in there and not leaving. And so that's what Locus
2:35
Speaker 2: is trying to do.
2:36
Speaker 1: That's the big dream. There's a narrower dream that I'm
2:39
Speaker 1: also interested in, yes, and that maybe a question that
2:44
Speaker 1: gets at the narrow dream is what are the limitations
2:49
Speaker 1: of antibiotics that you're trying to address.
2:52
Speaker 2: I think there are two things that are wrong with antibiotics.
2:55
Speaker 2: So one that most people are very, very familiar with
2:58
Speaker 2: is resistance is now everywhere, and so effectively we're beginning
3:05
Speaker 2: to see exponential increases in drug resists from almost all
3:11
Speaker 2: mainstream antibiotics, if not all. So there's sort of a
3:15
Speaker 2: math problem from here. At some point none of them
3:19
Speaker 2: work and the further up in strength you move in antibiotics,
3:26
Speaker 2: the more toxic they are to your body. And so
3:29
Speaker 2: if you're really sick and you have to go on
3:32
Speaker 2: a really strong antibiotic, the antibiotic itself can be your demise.
3:37
Speaker 2: So that's one thing. Another example might be people with
3:42
Speaker 2: recurrent ear infections or recurrent bladder infections end up going
3:46
Speaker 2: onto frequent batteries of antibiotics, say, you know, starting at
3:51
Speaker 2: fifteen days, but eventually getting the things like thirty days
3:55
Speaker 2: or forty five days of low volumes, and that can
3:59
Speaker 2: wreak havoc on your body. You know, it could basically
4:03
Speaker 2: destroy the balance in your microbiome. And you can have
4:07
Speaker 2: things that are long ranging side, like having to go
4:11
Speaker 2: on substantially simplistic diets for a long period of time
4:15
Speaker 2: because your intestinal track can't handle the variety of food
4:18
Speaker 2: that it likely needs for longevity. So those are just
4:22
Speaker 2: a couple of examples.
4:24
Speaker 1: Why my phages help to solve this problem.
4:28
Speaker 2: So we think that phases are one of the most
4:34
Speaker 2: unique and creative ways of getting into the human body
4:39
Speaker 2: to selectively attack a very specific bacterial pathogen or pathobian
4:47
Speaker 2: of interest, and only that particular target so I'm sure
4:51
Speaker 2: you've heard about precision medicine on the gene editing side
4:56
Speaker 2: for human cells that might be able to fix some
4:58
Speaker 2: of the world's roughest diseases. But on the bacterial side,
5:04
Speaker 2: precision medicine is quite new, And the idea of using
5:10
Speaker 2: phases as a delivery vector is essentially centering around the
5:16
Speaker 2: fact that they're exquisitely unique to the bacteria that they've
5:21
Speaker 2: evolved to infect. And so I think the largest, most
5:28
Speaker 2: abundant and oldest biological organism on the planet besides bacteria
5:35
Speaker 2: is faish.
5:36
Speaker 1: Yeah, that's amazing, right, Like the Earth is full of
5:38
Speaker 1: phases in the sea. When every day half of the
5:42
Speaker 1: bacteria and the sea get killed by stages or something like,
5:45
Speaker 1: it's wild, right, It's like it's incredible.
5:48
Speaker 2: Yeah, they say that half the bacteria on the planet,
5:51
Speaker 2: soil sea in Europe.
5:53
Speaker 1: Every day, Like it's happening all around us. It's happening
5:56
Speaker 1: inside our bodies, right, there are phases that naturally occur
5:58
Speaker 1: inside our.
5:58
Speaker 2: Bodies, and bacteria actually double at a very similar pace, right,
6:04
Speaker 2: So that this is one of nature's oldest and most
6:08
Speaker 2: established ecosystems.
6:10
Speaker 1: And this is an old idea it's super exciting when
6:13
Speaker 1: you hear it and they're like, oh wait, people have
6:15
Speaker 1: been trying to attack bacterial infection with phages for literally
6:19
Speaker 1: like one hundred years, right, and I haven't got that
6:23
Speaker 1: far with it. It sounds perfect. Why hasn't it worked
6:28
Speaker 1: that well so far?
6:29
Speaker 2: I think there are probably two or three reasons of note.
6:35
Speaker 2: One is that people essentially since i'd say a century
6:41
Speaker 2: ago when they were discovered, they use wild type phases,
6:46
Speaker 2: meaning they don't do any type of enhancement to that virus,
6:51
Speaker 2: They don't change the genome in any way. They simply
6:54
Speaker 2: search for one that is effectively a good killer in
6:57
Speaker 2: an academic lab, and then they take that killer and
7:01
Speaker 2: they put that into the human body expecting similar results.
7:05
Speaker 2: And you can see efficacylevels of those types of what
7:12
Speaker 2: we call wild type phase treatments in anywhere from fifty
7:17
Speaker 2: to maybe even sixty five maybe even in best cases
7:20
Speaker 2: seventy percent range, which you would say, well, that sounds decent,
7:26
Speaker 2: pretty good, But antibiotics have traditionally, up until when resistance
7:32
Speaker 2: has started to come into fray, those typically work around
7:36
Speaker 2: or above ninety five percent. So the efficacy difference between
7:42
Speaker 2: those two wild type phases and antibiotics is just so stark.
7:47
Speaker 2: In the days of the Cold War, antibiotics were not
7:52
Speaker 2: really available to people that were behind the Iron Curtain,
7:55
Speaker 2: and so face there be actually continued in many places
8:01
Speaker 2: inside Georgia, Russia, et cetera, and advanced into treatment centers
8:07
Speaker 2: that really were gear around a single phage for a
8:12
Speaker 2: single bacteria. And what that leads me to this sort
8:16
Speaker 2: of the second I think not shortcoming, but just natural
8:20
Speaker 2: component of phase, which is an individual PHASEE to go after.
8:27
Speaker 2: Let's say, a large population of bacteria in the human
8:30
Speaker 2: body will begin to see resistance.
8:33
Speaker 1: So that's the story of as you said, wild type
8:36
Speaker 1: phasi is naturally occurring phasis, you're doing something much more
8:40
Speaker 1: twenty first century right in a few ways. So we
8:43
Speaker 1: should introduce another sort of idea slash piece of jargon now, right,
8:49
Speaker 1: which is crisper cast three. People are used to think
8:53
Speaker 1: of crisper as like the gene scissors, right. I think
8:56
Speaker 1: people are relatively familiar with that, But this is a
8:59
Speaker 1: variant that is like the gene shredder, right, as opposed
9:02
Speaker 1: to a scissors.
9:03
Speaker 2: Yes, it works like essentially a pac Man if you
9:06
Speaker 2: remember the old arcade game. So it essentially makes a
9:10
Speaker 2: small nick in one strand of the DNA of the
9:14
Speaker 2: double helix, and then it choose that strand back by hundreds,
9:18
Speaker 2: if not thousands of base pairs to the point where
9:21
Speaker 2: it renders that that cell dead and by no means.
9:25
Speaker 2: And I think this is an evolution of our company
9:28
Speaker 2: and perhaps many others. Chrisper systems are not the only
9:31
Speaker 2: thing that you can engineer into a phage, Peptides, other enzymes,
9:35
Speaker 2: all kinds of things.
9:36
Speaker 1: Oh interesting, but that's I mean, just to be clear,
9:39
Speaker 1: Like the I call them drugs, they're drugs, rightugs. The
9:44
Speaker 1: drugs that you have in clinical trials are combining crisper
9:48
Speaker 1: cast three with a phage, right, Yes.
9:50
Speaker 2: Our lead asset is an E. Coli based product. It
9:54
Speaker 2: has six phases inside of that product, so it's a
9:59
Speaker 2: cocktail of phases and the majority of those phases are
10:04
Speaker 2: engineered to carry the entire crisper castori construct inside.
10:09
Speaker 1: So it's basically six different phases, each of which you've
10:12
Speaker 1: engineered to put on this gene shredder gene pac man.
10:16
Speaker 1: So the ideas the phases go into the infecting cells,
10:21
Speaker 1: the E coalie the bacteria, and then the Crisper eats
10:25
Speaker 1: up the DNA of those bacteria, thus killing the bacteria.
10:28
Speaker 1: That's the basic idea.
10:29
Speaker 2: That's the basic idea.
10:30
Speaker 1: So basically the idea is if you do a a
10:33
Speaker 1: bunch of different phases and b add to them something
10:38
Speaker 1: like Crisper casts three that makes it extra deadly, then
10:41
Speaker 1: you can clear the infection rather than just reducing.
10:44
Speaker 2: Correct.
10:45
Speaker 1: And so now you are running a clinical trial on
10:50
Speaker 1: women with recurrent urinary tract infections? Is that right?
10:53
Speaker 2: Correct?
10:54
Speaker 1: So tell me about that trial, like, where is it,
10:57
Speaker 1: what's happening, what's the you know, what's the outcome?
11:01
Speaker 2: Yeah. So we just does patient two hundred and twenty
11:05
Speaker 2: nine yesterday. We've got probably two hundred and eighty eight
11:11
Speaker 2: to maybe three hundred and eight patients that we're going
11:14
Speaker 2: to dose. And the idea is that it would not
11:18
Speaker 2: only deal with the acute infection that you're getting hit
11:22
Speaker 2: with right now, but it actually either eliminates or dramatically
11:28
Speaker 2: reduces the number of recurrent infections that you'll see in
11:31
Speaker 2: the future.
11:32
Speaker 1: Yeah, So tell me about like recurrent UTI as a problem.
11:37
Speaker 2: Inside the United States alone, over ten million people get
11:40
Speaker 2: recurrent infections, of which two million of that patient block
11:44
Speaker 2: get multiple recurrences. Once you get into a pattern of
11:48
Speaker 2: having multiple recurrences, it's very difficult to get rid of those.
11:53
Speaker 2: Many patients evolve through decades into a state of colonization,
12:00
Speaker 2: which just simply means that that bacteria embeds itself somewhere
12:04
Speaker 2: in your body and reinfections occur. You know, maybe for
12:08
Speaker 2: some a few times a year, but for many five
12:10
Speaker 2: six times a year.
12:12
Speaker 1: And how are you delivering the face treatment?
12:14
Speaker 2: So we have an intraor ethral delivery into the bladder,
12:18
Speaker 2: So we use a catheter, we avoid the bladder of
12:21
Speaker 2: its content, and then we reverse flow the drug product
12:24
Speaker 2: into the bladder, and in the process we also expand
12:27
Speaker 2: the bladder to make sure that the bladder wall is coded,
12:29
Speaker 2: and we hold the drug product there for about forty
12:34
Speaker 2: to fifty minutes before the patient's void. Again, we do
12:38
Speaker 2: that on the first day and the second day, and
12:40
Speaker 2: then simultaneously we have an intravenious backdrop that really is
12:46
Speaker 2: meant to try to get to the kidneys, and we
12:49
Speaker 2: do that on day one, two, and three, So the
12:52
Speaker 2: total time and duration is three days.
12:54
Speaker 1: So this is an intense treatment. This is like your
12:58
Speaker 1: uti would have to be extremely bad to want to
13:01
Speaker 1: do this.
13:02
Speaker 2: Frankly, you're in that two million patient population. And you know,
13:07
Speaker 2: if you had think about it this way, if you
13:10
Speaker 2: had a urinary track infection that was so bad that
13:12
Speaker 2: you had to stay home from work for three or
13:14
Speaker 2: four days until the antibiotics that you got called in
13:18
Speaker 2: for you kicked in, and then you were still under
13:20
Speaker 2: the weather for another six or seven days, and then
13:23
Speaker 2: at the end of that period, within a month to
13:25
Speaker 2: two months, you got another one, and those infections just
13:29
Speaker 2: in fact, when we talk to urologists and we talked
13:32
Speaker 2: to eurogynecologists, they say that this particular infection is the
13:38
Speaker 2: one that they feel the worst about for their patients
13:41
Speaker 2: over anything that they deal with, because there's nothing that
13:45
Speaker 2: they can really do about them except for treat them
13:48
Speaker 2: with antibiotics as the occurrences happen, and just keep giving
13:52
Speaker 2: them antibiotics every time they happen.
13:55
Speaker 1: What are the risks? What are the risks associated with
13:59
Speaker 1: the fish treatment?
14:00
Speaker 2: So we have not seen any crazy averse events, but
14:06
Speaker 2: the amount of viral particles that we put it into
14:09
Speaker 2: the body, some patients can get low grade fever, some
14:14
Speaker 2: patients can get a little nauseous.
14:16
Speaker 1: You're giving people a virus, right.
14:18
Speaker 2: You're giving a lot of virus.
14:21
Speaker 1: So when are you going to know if phase plus
14:26
Speaker 1: antibiotic works better than antibiotical one.
14:29
Speaker 2: So we should be finished dosing. We believe we'll be
14:32
Speaker 2: finished dosing sometime in the late fall to early winter,
14:36
Speaker 2: and then within ninety days from that last dose we'll
14:41
Speaker 2: have the data.
14:42
Speaker 1: So next less than a year. You should know.
14:45
Speaker 2: Definitely less than a year.
14:47
Speaker 1: So this UTI study is the one that's farthest along
14:52
Speaker 1: for you, what else do you have in clinical trials?
14:55
Speaker 2: So we have applied for an ID for a Crone's
15:00
Speaker 2: asset to try to essentially have an oral product that
15:06
Speaker 2: is similar to the UTI product but works more towards
15:10
Speaker 2: adherent invasive equal LIE, which is in many areas of medicine,
15:16
Speaker 2: considered to be at worst associative at best causal of
15:21
Speaker 2: Crohn's disease. In addition to that one, we're very close
15:25
Speaker 2: to being able to submit an I and D for
15:28
Speaker 2: this hospital acquired pneumonia asset, and that should be if
15:34
Speaker 2: we're on time, that one should get approved before the
15:37
Speaker 2: end of the year. So in theory, by the end
15:40
Speaker 2: of this year, in the beginning of next year, we
15:42
Speaker 2: would have three to four assets that we're moving through
15:45
Speaker 2: the clinic.
15:46
Speaker 1: And an asset is a drug. An asset's a drug,
15:49
Speaker 1: a drug that you own. That's why it's an asset
15:51
Speaker 1: for you.
15:51
Speaker 2: Well, in some cases partnered, but yes, one that we own.
15:55
Speaker 1: Or co own. Yeah, somebody owns. We'll be back in
16:02
Speaker 1: just a minute. Tell me about how you're using AI
16:17
Speaker 1: at your company.
16:18
Speaker 2: Yeah, so we use a what we call AI driven robotics,
16:24
Speaker 2: and so we discover phase at a volume I don't
16:28
Speaker 2: think anybody in the past has used. And then when
16:31
Speaker 2: we get those phage isolated, we sequence them, we run
16:36
Speaker 2: full characterization on them, and then we start running them
16:38
Speaker 2: through prediction engines that help us figure out what payloads
16:43
Speaker 2: to put into their genomes and which ones of those
16:46
Speaker 2: should go together and do a fixed drug.
16:48
Speaker 1: So, so let me just take a sec to understand
16:51
Speaker 1: that the prediction engines part, that second part that sounds
16:55
Speaker 1: like AI. But what's the robot part and how is
16:58
Speaker 1: it different than you know, what happens in a normal lab.
17:01
Speaker 2: Well, in a normal lab, you have a pipette, yeah
17:04
Speaker 2: kind of, Yeah, you have a little thumb thing that
17:09
Speaker 2: like depress and yeah, so you know discovering phases using
17:14
Speaker 2: sort of your regular old run of the mill.
17:16
Speaker 1: So what what So, okay, what are you doing.
17:19
Speaker 2: We're using hundreds, if not thousands, of ninety six well
17:23
Speaker 2: plates with the robot running twenty four hours a day,
17:27
Speaker 2: essentially looking at wastewater that we pull from all fifty
17:33
Speaker 2: states outside of international airports.
17:36
Speaker 1: Oh, you're doing outside of international airports because it's a
17:38
Speaker 1: more biodiverse sample, Like hundred percentages are flying in from
17:42
Speaker 1: all over the world in people's bodies in your samp
17:45
Speaker 1: Like that. I love that.
17:48
Speaker 2: Yeah, that's really cool.
17:49
Speaker 1: Would you say wastewater like you just go to like
17:51
Speaker 1: the sewer, Like, how do you actually do this?
17:54
Speaker 2: You reach out to the municipalities and you set up
17:59
Speaker 2: opportunities to pull them. And I mean in the early
18:02
Speaker 2: early days, we would go out there and we'd knock
18:04
Speaker 2: on the door and we'd askay can we do this?
18:07
Speaker 2: And in a lot of case as you can.
18:10
Speaker 1: And what's the order of magnitude of like how many
18:13
Speaker 1: different phases your your system is going through?
18:17
Speaker 2: So we have found it probably eighty five hundred uniquely identified,
18:23
Speaker 2: fully characterized phases against ninety nine different bacterial targets. So
18:28
Speaker 2: less size and scale that most academic labs, if not
18:32
Speaker 2: any academic lab could ever match.
18:35
Speaker 1: So then so that's that's the robot stage. And then
18:38
Speaker 1: you were saying, you move on to the to the
18:41
Speaker 1: kind of AI stage. What's that?
18:43
Speaker 2: So you maybe the best way to think about is
18:47
Speaker 2: it can work a little bit like Netflix. So if
18:50
Speaker 2: your you know, you watch a particular type of movie
18:53
Speaker 2: and there's a little algorithm behind the scenes that tries
18:56
Speaker 2: to figure out, well, what's the next best movie that's
18:59
Speaker 2: like that that you might want. And so we essentially
19:04
Speaker 2: apply very similar models to the sequenced information that we
19:09
Speaker 2: have on each of these unique phases, and we start
19:12
Speaker 2: to try to figure out, really by evaluating quadrillions of
19:16
Speaker 2: different options of pairing hundreds of not thousands of phase together,
19:20
Speaker 2: which one which four or five, six or seven of
19:23
Speaker 2: these go best together?
19:24
Speaker 1: So you want them to be complementary. You're targeting you're
19:27
Speaker 1: targeting some particular bacteria, and you're like, okay, give me
19:30
Speaker 1: the best cocktail correct AI.
19:33
Speaker 2: Yep. And then once it says try these top three,
19:36
Speaker 2: we go make them and then we grow it up
19:39
Speaker 2: and you know, manufacture small quantities of it, and then
19:42
Speaker 2: we test them out.
19:43
Speaker 1: And is that how you got the cocktails that are
19:45
Speaker 1: in trials now.
19:46
Speaker 2: The one that we have that's in trial now probably
19:51
Speaker 2: was a bit more manual because it's our first asset
19:53
Speaker 2: and it's probably built like seven years ago. The two,
19:57
Speaker 2: the three that we have that are coming this year,
20:00
Speaker 2: we're all built using that approach. So we're excited about
20:04
Speaker 2: the second generation assets that are going in.
20:08
Speaker 1: So so let's talk more long term, Like, let's talk
20:12
Speaker 1: about the sort of phase dream I've heard you talk about,
20:17
Speaker 1: you know, the potential that the kinds of things you're
20:19
Speaker 1: working on might go beyond what we think of as
20:22
Speaker 1: infectious disease someday. Tell me about the sort of big,
20:26
Speaker 1: big dream for phase treatment.
20:28
Speaker 2: I think crones sits in that arena for us. So
20:32
Speaker 2: Crone's disease is a immune disorder that essentially your body's
20:39
Speaker 2: immune system mistakes something in your intestinal track for an infection,
20:44
Speaker 2: and it targets your own intestinal organs and eats away
20:49
Speaker 2: at them to the point where you have small lesions
20:53
Speaker 2: that are actually in your intestinal lining. And what we
20:58
Speaker 2: know how to do in the field of medicine is
21:01
Speaker 2: essentially turned down the intensity of the attacking.
21:05
Speaker 1: So it's an autoimmune disorder. It's not thought of as
21:09
Speaker 1: infectious disease. Correct, So where does where does face therapy
21:14
Speaker 1: come in?
21:15
Speaker 2: In many circles of ib D, it's thought that bacteria
21:21
Speaker 2: is what the immune system is attacking.
21:23
Speaker 1: And IBD is inflammatory bowel disease. It's like that crones
21:27
Speaker 1: is one of.
21:27
Speaker 2: Your crones colitis variant forms of those anything that essentially
21:33
Speaker 2: diverticulated these types of things consider essentially intestinal organ disorders.
21:40
Speaker 2: There's a big umbrella term for IBD. And so many
21:44
Speaker 2: scientists believe that there are bacteria that gets stuck in
21:48
Speaker 2: there and are non transient, and it's those bacteria that
21:52
Speaker 2: get stuck in there and somehow adhere to the intestinal walls,
21:58
Speaker 2: that that is what the immune system is attacking.
22:01
Speaker 1: And that makes your immune system freak out and start
22:04
Speaker 1: attacking not just those cells but the bodies own cells.
22:07
Speaker 2: Correct. And so are drugs. And what we think is
22:11
Speaker 2: the holy grail of medicine is to be able to
22:14
Speaker 2: use phage encoded with payloads that can eat through either
22:18
Speaker 2: the biofilms, mucle layers or macrophage layers that protect those
22:23
Speaker 2: intracellular pathogens that our drugs would be able to get
22:27
Speaker 2: there precisely and kill just those pathogens, thereby causing the
22:33
Speaker 2: immune system to calm down and to potentially heal that
22:37
Speaker 2: patient with something that's curative.
22:41
Speaker 1: And just to be clear, is it the case that
22:44
Speaker 1: antibiotics just don't work for the particular the bacteria in
22:49
Speaker 1: the setting that you're describing.
22:50
Speaker 2: Antibiotics are known to not be able to kill intracellular pathogens.
22:55
Speaker 2: They can't transit into the human cells to kill the human.
22:58
Speaker 1: Cells, which is why they don't kill us.
23:01
Speaker 2: Presumably why antibiotics don't kill us. Yeah, presumably, I mean,
23:06
Speaker 2: that's one way to look at it.
23:08
Speaker 1: Absolutely, yeah, Yeah, And this is a trial that you're
23:13
Speaker 1: hoping you're hoping to sort of start a clinical trial
23:15
Speaker 1: based on this hypothesis. You said in the next year
23:18
Speaker 1: or so, we hope.
23:19
Speaker 2: To, We hope to. We still need to raise fund
23:22
Speaker 2: specifically for that one.
23:23
Speaker 1: I believe it less the way you say we hope to.
23:26
Speaker 2: Yeah, that when you're running a company like this, you
23:29
Speaker 2: tend to go where your contracts and partnerships are, and
23:32
Speaker 2: right now we have contracts in three of four areas,
23:35
Speaker 2: and so of course we're busy working on all three
23:38
Speaker 2: of those, and we hope to add the fourth.
23:41
Speaker 1: So what's the bigger idea here? Like, we kind of
23:44
Speaker 1: went far into the weeds on crumbs, But what is
23:46
Speaker 1: the bigger idea for you know, if you're right, like,
23:48
Speaker 1: what is the big hope for phaci therapy and whatever
23:51
Speaker 1: ten years or something.
23:53
Speaker 2: So I'll start high level and go down into that.
23:58
Speaker 2: Inflammation in the human body is not good. It causes
24:02
Speaker 2: many diseases without question, things like rumtory torte is potentially
24:07
Speaker 2: neuro disease is Things related to dementia, Parkinson's, etc. Like
24:13
Speaker 2: when inflammation occurs in certain sections of the body, bad
24:16
Speaker 2: things happen. Our hope for this platform is that it
24:20
Speaker 2: can reach into the human body via precision medicine and
24:24
Speaker 2: pull those pathogens or pathobians out.
24:28
Speaker 1: Is the underlying hypothesis that this sort of mysterious systemic
24:32
Speaker 1: inflammation is caused by particular kinds of bacterial infection.
24:36
Speaker 2: Yes, many pathogens that are in the body are bad actors.
24:41
Speaker 2: They're non transient, and the immune system is likely attacking
24:45
Speaker 2: those non transient bad actors. And so if you have
24:49
Speaker 2: a platform that can remove those bad actors, you likely
24:53
Speaker 2: also get the benefits of being able to improve the
24:57
Speaker 2: health of the human body, and that we believe will
25:01
Speaker 2: do things like increase the lives of most people in society.
25:07
Speaker 2: Or if you're genetically predisposed to a disease, you may
25:11
Speaker 2: be able to prevent the onset of that disease for
25:13
Speaker 2: a longer period of time. If you're genetically predisposed to
25:17
Speaker 2: a disease, you might be able to lessen the severity
25:20
Speaker 2: of that disease on your life. A good example might
25:24
Speaker 2: be rheumatory authritis. So if you remove pathogens that either
25:28
Speaker 2: aggravate or cause rhumatory authritis, can you help that patient
25:33
Speaker 2: with their symptomology. Can you decrease the pain that's associated
25:37
Speaker 2: in your joints with that disease by decreasing the amount
25:41
Speaker 2: of pathogens that you actually have in the body. We
25:44
Speaker 2: believe that that is a theory that is absolutely worth
25:49
Speaker 2: going after trying to figure out. And many people don't
25:53
Speaker 2: really realize this, but a lot of medicine is built
25:56
Speaker 2: on suppression. GOLP wants, autoimmune drugs. These things are basically
26:05
Speaker 2: shutting something down in the body to help a patient.
26:10
Speaker 2: They're not actually dealing with causes, and so hopefully also
26:13
Speaker 2: then we can start to talk about cures. But certainly
26:20
Speaker 2: if we're able to show direct causal relationships between certain
26:26
Speaker 2: pathogens that are in the body and improvement and disease symptomology,
26:31
Speaker 2: I think we're onto something really, really big.
26:37
Speaker 1: We'll be back in a minute with the liking round.
26:49
Speaker 1: What's your favorite phase?
26:51
Speaker 2: My favorite PHASEE?
26:53
Speaker 1: Yeah?
26:55
Speaker 2: Actually I really enjoy thinking about macrophages.
26:59
Speaker 1: Oh, the giant ones that they didn't even know where
27:01
Speaker 1: virus is because they're so big.
27:03
Speaker 2: Yeah, they tend to evolve really fast and move around
27:06
Speaker 2: on you, so it makes it a little bit interesting
27:08
Speaker 2: to figure out out how to actually pin one down
27:11
Speaker 2: and keep it from doing that when you don't want
27:13
Speaker 2: it to. But the possibilities of what you can load
27:16
Speaker 2: into a phase, the size of the payload that you
27:18
Speaker 2: could get in there, if you could replicate it, that's
27:22
Speaker 2: pretty exciting.
27:23
Speaker 1: So as a phase engineer, you're like, if we could
27:25
Speaker 1: tame that guy, we could stick anything in there.
27:27
Speaker 2: Yeah, I guess it'd be like taming a really big bull, right,
27:30
Speaker 2: Like what we get from that? I think the idea
27:33
Speaker 2: of being able to put all kinds of different peptides
27:37
Speaker 2: or other enzmatic tools into a phaseI and getting it
27:41
Speaker 2: very specifically into a certain part of the body and
27:43
Speaker 2: then having it in c too manufacture that payload right
27:47
Speaker 2: at the site where you want it. It's pretty fascinating
27:51
Speaker 2: as someone who's been in the industry for a number
27:53
Speaker 2: of decades. There's tons of good drugs that are on
27:57
Speaker 2: the shelf because of things like half life considerations, where
28:00
Speaker 2: it just doesn't stay alive and active long enough.
28:03
Speaker 1: Huh.
28:04
Speaker 2: But if you're manufacturing it in the body right where
28:06
Speaker 2: you need it with a phage, what can you do
28:09
Speaker 2: with those peptides that have long since been on the shelf.
28:12
Speaker 2: So I think there's some really cool things you can
28:15
Speaker 2: do with phases that are larger that might be able
28:18
Speaker 2: to carry some cool stuff.
28:21
Speaker 1: I heard you say that part of the reason you
28:23
Speaker 1: started a company was because you don't have a PhD.
28:26
Speaker 1: And you realize that in bigger companies there was just
28:28
Speaker 1: a ceiling on what you could do without a PhD.
28:31
Speaker 1: And I'm curious, have you found any advantages of not
28:38
Speaker 1: having a PhD. Does it give you any kind of
28:40
Speaker 1: a inside or edge that you might not have if
28:42
Speaker 1: you did have one.
28:43
Speaker 2: I mean, you can ask dumber questions of your team
28:46
Speaker 2: and get away with it. It sort of like why
28:48
Speaker 2: do you think that I don't understand? Explain that to me.
28:52
Speaker 1: That's actually I will say, that's my whole game. That's
28:55
Speaker 1: like my job is. It's like I don't understand that.
28:57
Speaker 1: Explained it to me.
28:58
Speaker 2: I also think that it gives us. It gives our
29:02
Speaker 2: culture inside of our company a bias towards more execution.
29:06
Speaker 2: And not that we're any less curious about scientific discovery,
29:10
Speaker 2: but once you pass a certain point where you're moving
29:14
Speaker 2: into the clinic and through the clinic, it's time to execute,
29:16
Speaker 2: and so you stay focused a little bit better.
29:19
Speaker 1: Right. You're an engineer by training, right, that's a very
29:22
Speaker 1: engineering mindset. Right, let's build a thing.
29:25
Speaker 2: Yeah, I'm a project manager by background. I'm a project manager.
29:28
Speaker 2: That's what I was. I guess raised doing is running
29:31
Speaker 2: huge projects.
29:34
Speaker 1: So you've been in biotech for what thirty more than
29:37
Speaker 1: thirty years, right, which is ye a long time. And
29:40
Speaker 1: I'm curious if you sort of look over the arc,
29:43
Speaker 1: if you go back to when you were starting, I'm
29:46
Speaker 1: curious what's surprising to you, Like, what has done better
29:50
Speaker 1: than you expected? What has done worse?
29:54
Speaker 2: That's a really no one's ever asked me that one before. Okay,
29:58
Speaker 2: I mean, I think on the better side, I really
30:03
Speaker 2: have been in awe and excited about cures I started.
30:10
Speaker 2: If you said, hey, we're working on a cure, people
30:13
Speaker 2: would look at you and you'd immediately be discredited.
30:17
Speaker 1: So what can we cure now that we couldn't cure
30:19
Speaker 1: when you started?
30:20
Speaker 2: I don't think you necessarily have all of the cures
30:23
Speaker 2: for things like do Chanes or Parkinson's or Alzheimer's that.
30:28
Speaker 1: Are definitely not for those, But what can we cure?
30:32
Speaker 2: I think they're I think they're coming. And that's that's
30:36
Speaker 2: my answer to your question of what's really cool about
30:38
Speaker 2: biotech the hard parts, the parts that maybe aren't so
30:42
Speaker 2: fun is I think we had just a huge bullet
30:46
Speaker 2: of garbage ideas that flooded into the industry post COVID.
30:51
Speaker 2: The amount of money that came into the industry post COVID,
30:54
Speaker 2: the craze around SPACs. It basically drained all the talent
30:59
Speaker 2: into a bunch of BS companies, and it took a
31:01
Speaker 2: couple of years for that to flood out.
31:03
Speaker 1: The curse of too much money. It's funny people mention
31:06
Speaker 1: that more often than I would have thought.
31:09
Speaker 2: In an industry that's used to creating four hundred companies
31:12
Speaker 2: per year. You don't want to create four thousand for two.
31:15
Speaker 2: And that's not you just don't have the talent enough
31:20
Speaker 2: in the executive and leadership ranks to hold that. And
31:23
Speaker 2: where you get that from as your service partners, you're
31:26
Speaker 2: your vendors, and then your vendors don't know what they're doing.
31:30
Speaker 2: And so we had to live through that. I think
31:32
Speaker 2: we're through that. I actually think we're on the other
31:34
Speaker 2: side of that, which is I guess time will tell
31:37
Speaker 2: as we see what actually breaks through.
31:46
Speaker 1: Paul Gariffolo is the co founder and CEO of Locust Biosciences.
31:52
Speaker 1: Please let us know what you think of the show.
31:55
Speaker 1: Do you want to hear more of, which you want
31:56
Speaker 1: to hear less of? Would you go guest ideas? You
32:00
Speaker 1: can email us at problem at pushkin dot fm. I
32:03
Speaker 1: read all the emails. You can also find me on
32:06
Speaker 1: x LinkedIn. Do appreciate all the messages that we get.
32:12
Speaker 1: Today's show was produced by Gabriel Hunter Chang and Trina Menino.
32:15
Speaker 1: It was engineered by Hans Dale She and edited by
32:18
Speaker 1: Lydia Jean Kott. I'm Jacob Goldstein and we'll be back
32:21
Speaker 1: next week with another episode of What's Your Problem,