WEBVTT - Using Viruses to Fight Disease 0:00:15.356 --> 0:00:24.836 Pushkin. I love phages. Phages are viruses that attack bacteria. 0:00:25.796 --> 0:00:32.596 Phages are unimaginably abundant, a trillion phages for every grain 0:00:32.676 --> 0:00:36.796 of sand on Earth, according to one estimate, which what 0:00:36.836 --> 0:00:40.796 does that even mean? Qualitatively? It means phages are all 0:00:40.836 --> 0:00:44.236 around us, they are inside of us, They're essential to 0:00:44.316 --> 0:00:48.636 life on earth, and they may help to improve human 0:00:48.716 --> 0:01:03.676 health in a profound way. I'm Jacob Goldstein. This is 0:01:03.676 --> 0:01:07.236 what's your problem? And my guest today is Paul Garifolo. 0:01:07.636 --> 0:01:09.916 He is the co founder and CEO of a company 0:01:09.956 --> 0:01:14.876 called Locust Biosciences. Paul's problem is this, can you use 0:01:15.076 --> 0:01:20.396 genetically engineered phages to cure disease? People have been trying 0:01:20.396 --> 0:01:23.756 to use phages to cure infections for over one hundred 0:01:23.836 --> 0:01:28.436 years now, but in most cases, naturally occurring phages just 0:01:28.596 --> 0:01:33.916 don't work as well as antibiotics as drugs. Phages reduce infections, 0:01:33.956 --> 0:01:37.396 but they often don't wipe them out entirely. So Paul 0:01:37.436 --> 0:01:40.876 and his colleagues are taking a different approach. They're genetically 0:01:40.956 --> 0:01:45.516 engineering phages to make them better at killing bacteria. For now, 0:01:45.676 --> 0:01:49.316 the company is testing its first phage based drug in 0:01:49.516 --> 0:01:53.996 patients in combination with antibiotics. But Paul says, the long 0:01:54.076 --> 0:01:55.716 term dream is bigger than that. 0:01:56.436 --> 0:02:00.956 So we actually have been trying to figure out how 0:02:00.996 --> 0:02:07.156 to selectively remove bacteria from the human body without touching 0:02:07.196 --> 0:02:10.036 any of the good bacteria that's in there, and we 0:02:10.156 --> 0:02:15.476 believe that that is a key to longevity of human life. 0:02:16.756 --> 0:02:21.356 We're starting with trying to replace antibiotics, but we believe 0:02:21.476 --> 0:02:25.076 that any number of diseases in the human body or 0:02:25.236 --> 0:02:31.676 actually the body's reaction to inflammation from bad bacteria getting 0:02:31.676 --> 0:02:34.996 in there and not leaving. And so that's what Locus 0:02:35.076 --> 0:02:35.716 is trying to do. 0:02:36.676 --> 0:02:39.476 That's the big dream. There's a narrower dream that I'm 0:02:39.476 --> 0:02:44.276 also interested in, yes, and that maybe a question that 0:02:44.316 --> 0:02:49.156 gets at the narrow dream is what are the limitations 0:02:49.196 --> 0:02:51.956 of antibiotics that you're trying to address. 0:02:52.236 --> 0:02:55.596 I think there are two things that are wrong with antibiotics. 0:02:55.756 --> 0:02:58.716 So one that most people are very, very familiar with 0:02:58.876 --> 0:03:05.236 is resistance is now everywhere, and so effectively we're beginning 0:03:05.236 --> 0:03:11.196 to see exponential increases in drug resists from almost all 0:03:11.276 --> 0:03:15.956 mainstream antibiotics, if not all. So there's sort of a 0:03:15.996 --> 0:03:19.156 math problem from here. At some point none of them 0:03:19.196 --> 0:03:26.036 work and the further up in strength you move in antibiotics, 0:03:26.036 --> 0:03:29.276 the more toxic they are to your body. And so 0:03:29.396 --> 0:03:32.236 if you're really sick and you have to go on 0:03:32.316 --> 0:03:37.316 a really strong antibiotic, the antibiotic itself can be your demise. 0:03:37.476 --> 0:03:41.996 So that's one thing. Another example might be people with 0:03:42.116 --> 0:03:46.796 recurrent ear infections or recurrent bladder infections end up going 0:03:46.876 --> 0:03:51.836 onto frequent batteries of antibiotics, say, you know, starting at 0:03:51.836 --> 0:03:55.196 fifteen days, but eventually getting the things like thirty days 0:03:55.276 --> 0:03:58.956 or forty five days of low volumes, and that can 0:03:59.116 --> 0:04:03.396 wreak havoc on your body. You know, it could basically 0:04:03.436 --> 0:04:07.116 destroy the balance in your microbiome. And you can have 0:04:07.236 --> 0:04:11.116 things that are long ranging side, like having to go 0:04:11.196 --> 0:04:15.156 on substantially simplistic diets for a long period of time 0:04:15.196 --> 0:04:18.796 because your intestinal track can't handle the variety of food 0:04:18.836 --> 0:04:22.716 that it likely needs for longevity. So those are just 0:04:22.756 --> 0:04:24.396 a couple of examples. 0:04:24.356 --> 0:04:27.596 Why my phages help to solve this problem. 0:04:28.276 --> 0:04:33.036 So we think that phases are one of the most 0:04:34.636 --> 0:04:39.396 unique and creative ways of getting into the human body 0:04:39.596 --> 0:04:46.996 to selectively attack a very specific bacterial pathogen or pathobian 0:04:47.196 --> 0:04:51.836 of interest, and only that particular target so I'm sure 0:04:51.876 --> 0:04:56.476 you've heard about precision medicine on the gene editing side 0:04:56.516 --> 0:04:58.876 for human cells that might be able to fix some 0:04:58.916 --> 0:05:04.716 of the world's roughest diseases. But on the bacterial side, 0:05:04.796 --> 0:05:10.396 precision medicine is quite new, And the idea of using 0:05:10.596 --> 0:05:16.956 phases as a delivery vector is essentially centering around the 0:05:16.996 --> 0:05:21.316 fact that they're exquisitely unique to the bacteria that they've 0:05:21.356 --> 0:05:28.076 evolved to infect. And so I think the largest, most 0:05:28.116 --> 0:05:34.836 abundant and oldest biological organism on the planet besides bacteria 0:05:35.076 --> 0:05:35.556 is faish. 0:05:36.276 --> 0:05:38.396 Yeah, that's amazing, right, Like the Earth is full of 0:05:38.436 --> 0:05:42.436 phases in the sea. When every day half of the 0:05:42.476 --> 0:05:45.076 bacteria and the sea get killed by stages or something like, 0:05:45.156 --> 0:05:47.876 it's wild, right, It's like it's incredible. 0:05:48.116 --> 0:05:50.996 Yeah, they say that half the bacteria on the planet, 0:05:51.076 --> 0:05:53.596 soil sea in Europe. 0:05:53.196 --> 0:05:56.116 Every day, Like it's happening all around us. It's happening 0:05:56.156 --> 0:05:58.516 inside our bodies, right, there are phases that naturally occur 0:05:58.556 --> 0:05:59.036 inside our. 0:05:58.916 --> 0:06:04.276 Bodies, and bacteria actually double at a very similar pace, right, 0:06:04.356 --> 0:06:08.556 So that this is one of nature's oldest and most 0:06:08.636 --> 0:06:10.396 established ecosystems. 0:06:10.716 --> 0:06:13.796 And this is an old idea it's super exciting when 0:06:13.796 --> 0:06:15.356 you hear it and they're like, oh wait, people have 0:06:15.396 --> 0:06:19.516 been trying to attack bacterial infection with phages for literally 0:06:19.556 --> 0:06:22.836 like one hundred years, right, and I haven't got that 0:06:23.156 --> 0:06:28.276 far with it. It sounds perfect. Why hasn't it worked 0:06:28.476 --> 0:06:29.636 that well so far? 0:06:29.836 --> 0:06:35.396 I think there are probably two or three reasons of note. 0:06:35.676 --> 0:06:41.556 One is that people essentially since i'd say a century 0:06:41.556 --> 0:06:45.076 ago when they were discovered, they use wild type phases, 0:06:46.436 --> 0:06:51.076 meaning they don't do any type of enhancement to that virus, 0:06:51.116 --> 0:06:53.956 They don't change the genome in any way. They simply 0:06:54.036 --> 0:06:57.556 search for one that is effectively a good killer in 0:06:57.596 --> 0:07:01.396 an academic lab, and then they take that killer and 0:07:01.476 --> 0:07:04.876 they put that into the human body expecting similar results. 0:07:05.676 --> 0:07:12.116 And you can see efficacylevels of those types of what 0:07:12.156 --> 0:07:17.316 we call wild type phase treatments in anywhere from fifty 0:07:17.516 --> 0:07:20.956 to maybe even sixty five maybe even in best cases 0:07:20.996 --> 0:07:25.476 seventy percent range, which you would say, well, that sounds decent, 0:07:26.116 --> 0:07:32.676 pretty good, But antibiotics have traditionally, up until when resistance 0:07:32.716 --> 0:07:36.716 has started to come into fray, those typically work around 0:07:36.836 --> 0:07:41.996 or above ninety five percent. So the efficacy difference between 0:07:42.036 --> 0:07:46.596 those two wild type phases and antibiotics is just so stark. 0:07:47.356 --> 0:07:52.436 In the days of the Cold War, antibiotics were not 0:07:52.556 --> 0:07:55.796 really available to people that were behind the Iron Curtain, 0:07:55.916 --> 0:08:01.036 and so face there be actually continued in many places 0:08:01.076 --> 0:08:06.996 inside Georgia, Russia, et cetera, and advanced into treatment centers 0:08:07.116 --> 0:08:12.076 that really were gear around a single phage for a 0:08:12.116 --> 0:08:16.076 single bacteria. And what that leads me to this sort 0:08:16.076 --> 0:08:19.916 of the second I think not shortcoming, but just natural 0:08:20.716 --> 0:08:27.116 component of phase, which is an individual PHASEE to go after. 0:08:27.276 --> 0:08:30.356 Let's say, a large population of bacteria in the human 0:08:30.356 --> 0:08:32.396 body will begin to see resistance. 0:08:33.116 --> 0:08:35.956 So that's the story of as you said, wild type 0:08:36.196 --> 0:08:40.116 phasi is naturally occurring phasis, you're doing something much more 0:08:40.716 --> 0:08:43.876 twenty first century right in a few ways. So we 0:08:43.916 --> 0:08:49.116 should introduce another sort of idea slash piece of jargon now, right, 0:08:49.156 --> 0:08:53.436 which is crisper cast three. People are used to think 0:08:53.476 --> 0:08:56.876 of crisper as like the gene scissors, right. I think 0:08:56.916 --> 0:08:59.036 people are relatively familiar with that, But this is a 0:08:59.156 --> 0:09:02.796 variant that is like the gene shredder, right, as opposed 0:09:02.836 --> 0:09:03.476 to a scissors. 0:09:03.756 --> 0:09:06.756 Yes, it works like essentially a pac Man if you 0:09:06.876 --> 0:09:10.436 remember the old arcade game. So it essentially makes a 0:09:10.476 --> 0:09:14.756 small nick in one strand of the DNA of the 0:09:14.796 --> 0:09:18.676 double helix, and then it choose that strand back by hundreds, 0:09:18.676 --> 0:09:21.236 if not thousands of base pairs to the point where 0:09:21.276 --> 0:09:25.636 it renders that that cell dead and by no means. 0:09:25.796 --> 0:09:28.636 And I think this is an evolution of our company 0:09:28.676 --> 0:09:31.756 and perhaps many others. Chrisper systems are not the only 0:09:31.796 --> 0:09:35.796 thing that you can engineer into a phage, Peptides, other enzymes, 0:09:35.836 --> 0:09:36.476 all kinds of things. 0:09:36.636 --> 0:09:39.516 Oh interesting, but that's I mean, just to be clear, 0:09:39.756 --> 0:09:44.276 Like the I call them drugs, they're drugs, rightugs. The 0:09:44.356 --> 0:09:48.516 drugs that you have in clinical trials are combining crisper 0:09:48.556 --> 0:09:50.836 cast three with a phage, right, Yes. 0:09:50.756 --> 0:09:54.836 Our lead asset is an E. Coli based product. It 0:09:54.876 --> 0:09:59.036 has six phases inside of that product, so it's a 0:09:59.076 --> 0:10:04.236 cocktail of phases and the majority of those phases are 0:10:04.236 --> 0:10:09.236 engineered to carry the entire crisper castori construct inside. 0:10:09.476 --> 0:10:12.956 So it's basically six different phases, each of which you've 0:10:12.996 --> 0:10:16.836 engineered to put on this gene shredder gene pac man. 0:10:16.916 --> 0:10:21.756 So the ideas the phases go into the infecting cells, 0:10:21.756 --> 0:10:25.276 the E coalie the bacteria, and then the Crisper eats 0:10:25.356 --> 0:10:28.596 up the DNA of those bacteria, thus killing the bacteria. 0:10:28.676 --> 0:10:29.716 That's the basic idea. 0:10:29.756 --> 0:10:30.676 That's the basic idea. 0:10:30.836 --> 0:10:33.716 So basically the idea is if you do a a 0:10:33.756 --> 0:10:38.036 bunch of different phases and b add to them something 0:10:38.076 --> 0:10:41.076 like Crisper casts three that makes it extra deadly, then 0:10:41.156 --> 0:10:44.316 you can clear the infection rather than just reducing. 0:10:44.396 --> 0:10:44.796 Correct. 0:10:45.436 --> 0:10:49.116 And so now you are running a clinical trial on 0:10:50.316 --> 0:10:53.476 women with recurrent urinary tract infections? Is that right? 0:10:53.756 --> 0:10:54.196 Correct? 0:10:54.716 --> 0:10:57.836 So tell me about that trial, like, where is it, 0:10:57.956 --> 0:11:01.116 what's happening, what's the you know, what's the outcome? 0:11:01.516 --> 0:11:05.236 Yeah. So we just does patient two hundred and twenty 0:11:05.356 --> 0:11:11.476 nine yesterday. We've got probably two hundred and eighty eight 0:11:11.596 --> 0:11:14.516 to maybe three hundred and eight patients that we're going 0:11:14.556 --> 0:11:18.196 to dose. And the idea is that it would not 0:11:18.356 --> 0:11:22.316 only deal with the acute infection that you're getting hit 0:11:22.436 --> 0:11:27.996 with right now, but it actually either eliminates or dramatically 0:11:28.036 --> 0:11:31.556 reduces the number of recurrent infections that you'll see in 0:11:31.596 --> 0:11:32.116 the future. 0:11:32.716 --> 0:11:36.796 Yeah, So tell me about like recurrent UTI as a problem. 0:11:37.036 --> 0:11:40.476 Inside the United States alone, over ten million people get 0:11:40.516 --> 0:11:44.316 recurrent infections, of which two million of that patient block 0:11:44.476 --> 0:11:48.956 get multiple recurrences. Once you get into a pattern of 0:11:48.996 --> 0:11:53.316 having multiple recurrences, it's very difficult to get rid of those. 0:11:53.956 --> 0:11:59.476 Many patients evolve through decades into a state of colonization, 0:12:00.116 --> 0:12:04.156 which just simply means that that bacteria embeds itself somewhere 0:12:04.156 --> 0:12:07.996 in your body and reinfections occur. You know, maybe for 0:12:08.116 --> 0:12:10.676 some a few times a year, but for many five 0:12:10.796 --> 0:12:11.756 six times a year. 0:12:12.116 --> 0:12:13.956 And how are you delivering the face treatment? 0:12:14.156 --> 0:12:18.476 So we have an intraor ethral delivery into the bladder, 0:12:18.556 --> 0:12:21.316 So we use a catheter, we avoid the bladder of 0:12:21.356 --> 0:12:24.116 its content, and then we reverse flow the drug product 0:12:24.196 --> 0:12:27.396 into the bladder, and in the process we also expand 0:12:27.396 --> 0:12:29.876 the bladder to make sure that the bladder wall is coded, 0:12:29.916 --> 0:12:34.396 and we hold the drug product there for about forty 0:12:34.436 --> 0:12:37.956 to fifty minutes before the patient's void. Again, we do 0:12:38.076 --> 0:12:40.836 that on the first day and the second day, and 0:12:40.876 --> 0:12:46.116 then simultaneously we have an intravenious backdrop that really is 0:12:46.196 --> 0:12:49.556 meant to try to get to the kidneys, and we 0:12:49.636 --> 0:12:52.196 do that on day one, two, and three, So the 0:12:52.276 --> 0:12:54.636 total time and duration is three days. 0:12:54.876 --> 0:12:58.676 So this is an intense treatment. This is like your 0:12:58.796 --> 0:13:01.996 uti would have to be extremely bad to want to 0:13:01.996 --> 0:13:02.276 do this. 0:13:02.356 --> 0:13:07.876 Frankly, you're in that two million patient population. And you know, 0:13:07.916 --> 0:13:10.356 if you had think about it this way, if you 0:13:10.356 --> 0:13:12.876 had a urinary track infection that was so bad that 0:13:12.916 --> 0:13:14.956 you had to stay home from work for three or 0:13:14.956 --> 0:13:18.076 four days until the antibiotics that you got called in 0:13:18.156 --> 0:13:20.676 for you kicked in, and then you were still under 0:13:20.716 --> 0:13:23.316 the weather for another six or seven days, and then 0:13:23.396 --> 0:13:25.876 at the end of that period, within a month to 0:13:25.956 --> 0:13:29.556 two months, you got another one, and those infections just 0:13:29.876 --> 0:13:32.316 in fact, when we talk to urologists and we talked 0:13:32.356 --> 0:13:38.196 to eurogynecologists, they say that this particular infection is the 0:13:38.236 --> 0:13:41.676 one that they feel the worst about for their patients 0:13:41.716 --> 0:13:45.556 over anything that they deal with, because there's nothing that 0:13:45.596 --> 0:13:48.396 they can really do about them except for treat them 0:13:48.436 --> 0:13:52.996 with antibiotics as the occurrences happen, and just keep giving 0:13:52.996 --> 0:13:55.316 them antibiotics every time they happen. 0:13:55.996 --> 0:13:58.676 What are the risks? What are the risks associated with 0:13:59.236 --> 0:14:00.156 the fish treatment? 0:14:00.596 --> 0:14:05.916 So we have not seen any crazy averse events, but 0:14:06.156 --> 0:14:09.516 the amount of viral particles that we put it into 0:14:09.516 --> 0:14:14.276 the body, some patients can get low grade fever, some 0:14:14.476 --> 0:14:16.676 patients can get a little nauseous. 0:14:16.836 --> 0:14:18.876 You're giving people a virus, right. 0:14:18.956 --> 0:14:21.036 You're giving a lot of virus. 0:14:21.396 --> 0:14:26.516 So when are you going to know if phase plus 0:14:26.556 --> 0:14:28.756 antibiotic works better than antibiotical one. 0:14:29.276 --> 0:14:32.836 So we should be finished dosing. We believe we'll be 0:14:32.876 --> 0:14:36.556 finished dosing sometime in the late fall to early winter, 0:14:36.916 --> 0:14:41.436 and then within ninety days from that last dose we'll 0:14:41.436 --> 0:14:42.076 have the data. 0:14:42.716 --> 0:14:45.676 So next less than a year. You should know. 0:14:45.836 --> 0:14:47.196 Definitely less than a year. 0:14:47.756 --> 0:14:51.956 So this UTI study is the one that's farthest along 0:14:52.356 --> 0:14:55.676 for you, what else do you have in clinical trials? 0:14:55.796 --> 0:15:00.956 So we have applied for an ID for a Crone's 0:15:00.996 --> 0:15:05.996 asset to try to essentially have an oral product that 0:15:06.356 --> 0:15:10.836 is similar to the UTI product but works more towards 0:15:10.916 --> 0:15:15.956 adherent invasive equal LIE, which is in many areas of medicine, 0:15:16.116 --> 0:15:21.236 considered to be at worst associative at best causal of 0:15:21.396 --> 0:15:25.836 Crohn's disease. In addition to that one, we're very close 0:15:25.876 --> 0:15:28.156 to being able to submit an I and D for 0:15:28.316 --> 0:15:34.236 this hospital acquired pneumonia asset, and that should be if 0:15:34.276 --> 0:15:37.636 we're on time, that one should get approved before the 0:15:37.756 --> 0:15:40.396 end of the year. So in theory, by the end 0:15:40.436 --> 0:15:42.916 of this year, in the beginning of next year, we 0:15:42.956 --> 0:15:45.596 would have three to four assets that we're moving through 0:15:45.676 --> 0:15:46.196 the clinic. 0:15:46.436 --> 0:15:48.516 And an asset is a drug. An asset's a drug, 0:15:49.036 --> 0:15:51.116 a drug that you own. That's why it's an asset 0:15:51.156 --> 0:15:51.396 for you. 0:15:51.556 --> 0:15:55.716 Well, in some cases partnered, but yes, one that we own. 0:15:55.836 --> 0:16:02.196 Or co own. Yeah, somebody owns. We'll be back in 0:16:02.316 --> 0:16:16.796 just a minute. Tell me about how you're using AI 0:16:17.076 --> 0:16:17.796 at your company. 0:16:18.236 --> 0:16:23.876 Yeah, so we use a what we call AI driven robotics, 0:16:24.236 --> 0:16:28.636 and so we discover phase at a volume I don't 0:16:28.676 --> 0:16:31.436 think anybody in the past has used. And then when 0:16:31.476 --> 0:16:36.156 we get those phage isolated, we sequence them, we run 0:16:36.196 --> 0:16:38.676 full characterization on them, and then we start running them 0:16:38.676 --> 0:16:43.396 through prediction engines that help us figure out what payloads 0:16:43.436 --> 0:16:46.356 to put into their genomes and which ones of those 0:16:46.396 --> 0:16:48.276 should go together and do a fixed drug. 0:16:48.836 --> 0:16:51.036 So, so let me just take a sec to understand 0:16:51.036 --> 0:16:55.196 that the prediction engines part, that second part that sounds 0:16:55.236 --> 0:16:58.076 like AI. But what's the robot part and how is 0:16:58.116 --> 0:17:00.716 it different than you know, what happens in a normal lab. 0:17:01.276 --> 0:17:04.116 Well, in a normal lab, you have a pipette, yeah 0:17:04.316 --> 0:17:08.796 kind of, Yeah, you have a little thumb thing that 0:17:09.316 --> 0:17:13.956 like depress and yeah, so you know discovering phases using 0:17:14.396 --> 0:17:16.516 sort of your regular old run of the mill. 0:17:16.676 --> 0:17:19.036 So what what So, okay, what are you doing. 0:17:19.476 --> 0:17:23.796 We're using hundreds, if not thousands, of ninety six well 0:17:23.836 --> 0:17:27.276 plates with the robot running twenty four hours a day, 0:17:27.516 --> 0:17:33.116 essentially looking at wastewater that we pull from all fifty 0:17:33.156 --> 0:17:35.556 states outside of international airports. 0:17:36.036 --> 0:17:38.716 Oh, you're doing outside of international airports because it's a 0:17:38.756 --> 0:17:42.716 more biodiverse sample, Like hundred percentages are flying in from 0:17:42.756 --> 0:17:45.636 all over the world in people's bodies in your samp 0:17:45.756 --> 0:17:48.036 Like that. I love that. 0:17:48.116 --> 0:17:48.956 Yeah, that's really cool. 0:17:49.316 --> 0:17:51.316 Would you say wastewater like you just go to like 0:17:51.356 --> 0:17:54.836 the sewer, Like, how do you actually do this? 0:17:54.996 --> 0:17:58.236 You reach out to the municipalities and you set up 0:17:59.036 --> 0:18:02.116 opportunities to pull them. And I mean in the early 0:18:02.196 --> 0:18:04.716 early days, we would go out there and we'd knock 0:18:04.756 --> 0:18:07.356 on the door and we'd askay can we do this? 0:18:07.956 --> 0:18:09.996 And in a lot of case as you can. 0:18:10.356 --> 0:18:13.596 And what's the order of magnitude of like how many 0:18:13.636 --> 0:18:16.756 different phases your your system is going through? 0:18:17.116 --> 0:18:22.916 So we have found it probably eighty five hundred uniquely identified, 0:18:23.036 --> 0:18:28.636 fully characterized phases against ninety nine different bacterial targets. So 0:18:28.796 --> 0:18:32.276 less size and scale that most academic labs, if not 0:18:32.356 --> 0:18:34.276 any academic lab could ever match. 0:18:35.156 --> 0:18:38.636 So then so that's that's the robot stage. And then 0:18:38.676 --> 0:18:41.196 you were saying, you move on to the to the 0:18:41.556 --> 0:18:42.956 kind of AI stage. What's that? 0:18:43.716 --> 0:18:46.916 So you maybe the best way to think about is 0:18:47.036 --> 0:18:50.556 it can work a little bit like Netflix. So if 0:18:50.596 --> 0:18:53.276 your you know, you watch a particular type of movie 0:18:53.356 --> 0:18:56.956 and there's a little algorithm behind the scenes that tries 0:18:56.996 --> 0:18:59.796 to figure out, well, what's the next best movie that's 0:18:59.916 --> 0:19:03.996 like that that you might want. And so we essentially 0:19:04.036 --> 0:19:09.196 apply very similar models to the sequenced information that we 0:19:09.036 --> 0:19:12.076 have on each of these unique phases, and we start 0:19:12.076 --> 0:19:16.276 to try to figure out, really by evaluating quadrillions of 0:19:16.316 --> 0:19:20.676 different options of pairing hundreds of not thousands of phase together, 0:19:20.796 --> 0:19:23.236 which one which four or five, six or seven of 0:19:23.276 --> 0:19:24.516 these go best together? 0:19:24.916 --> 0:19:27.876 So you want them to be complementary. You're targeting you're 0:19:27.876 --> 0:19:30.876 targeting some particular bacteria, and you're like, okay, give me 0:19:30.916 --> 0:19:32.676 the best cocktail correct AI. 0:19:33.036 --> 0:19:35.916 Yep. And then once it says try these top three, 0:19:36.156 --> 0:19:39.476 we go make them and then we grow it up 0:19:39.516 --> 0:19:42.196 and you know, manufacture small quantities of it, and then 0:19:42.236 --> 0:19:43.156 we test them out. 0:19:43.276 --> 0:19:45.276 And is that how you got the cocktails that are 0:19:45.316 --> 0:19:46.396 in trials now. 0:19:46.996 --> 0:19:51.236 The one that we have that's in trial now probably 0:19:51.316 --> 0:19:53.636 was a bit more manual because it's our first asset 0:19:53.836 --> 0:19:57.156 and it's probably built like seven years ago. The two, 0:19:57.836 --> 0:20:00.116 the three that we have that are coming this year, 0:20:00.276 --> 0:20:04.876 we're all built using that approach. So we're excited about 0:20:04.916 --> 0:20:07.396 the second generation assets that are going in. 0:20:08.516 --> 0:20:12.196 So so let's talk more long term, Like, let's talk 0:20:12.236 --> 0:20:17.236 about the sort of phase dream I've heard you talk about, 0:20:17.596 --> 0:20:19.716 you know, the potential that the kinds of things you're 0:20:19.756 --> 0:20:22.636 working on might go beyond what we think of as 0:20:22.636 --> 0:20:26.196 infectious disease someday. Tell me about the sort of big, 0:20:26.316 --> 0:20:28.476 big dream for phase treatment. 0:20:28.756 --> 0:20:32.076 I think crones sits in that arena for us. So 0:20:32.876 --> 0:20:39.316 Crone's disease is a immune disorder that essentially your body's 0:20:39.396 --> 0:20:44.316 immune system mistakes something in your intestinal track for an infection, 0:20:44.596 --> 0:20:49.796 and it targets your own intestinal organs and eats away 0:20:49.836 --> 0:20:52.876 at them to the point where you have small lesions 0:20:53.476 --> 0:20:57.956 that are actually in your intestinal lining. And what we 0:20:58.116 --> 0:21:00.196 know how to do in the field of medicine is 0:21:01.076 --> 0:21:05.236 essentially turned down the intensity of the attacking. 0:21:05.796 --> 0:21:08.996 So it's an autoimmune disorder. It's not thought of as 0:21:09.756 --> 0:21:14.476 infectious disease. Correct, So where does where does face therapy 0:21:14.516 --> 0:21:15.156 come in? 0:21:15.156 --> 0:21:20.356 In many circles of ib D, it's thought that bacteria 0:21:21.156 --> 0:21:23.716 is what the immune system is attacking. 0:21:23.636 --> 0:21:27.316 And IBD is inflammatory bowel disease. It's like that crones 0:21:27.396 --> 0:21:27.636 is one of. 0:21:27.636 --> 0:21:33.556 Your crones colitis variant forms of those anything that essentially 0:21:33.716 --> 0:21:39.436 diverticulated these types of things consider essentially intestinal organ disorders. 0:21:40.396 --> 0:21:44.756 There's a big umbrella term for IBD. And so many 0:21:44.796 --> 0:21:48.476 scientists believe that there are bacteria that gets stuck in 0:21:48.516 --> 0:21:52.916 there and are non transient, and it's those bacteria that 0:21:52.996 --> 0:21:57.036 get stuck in there and somehow adhere to the intestinal walls, 0:21:58.556 --> 0:22:02.036 that that is what the immune system is attacking. 0:22:01.556 --> 0:22:04.476 And that makes your immune system freak out and start 0:22:04.556 --> 0:22:07.356 attacking not just those cells but the bodies own cells. 0:22:07.516 --> 0:22:11.396 Correct. And so are drugs. And what we think is 0:22:11.476 --> 0:22:14.036 the holy grail of medicine is to be able to 0:22:14.116 --> 0:22:18.556 use phage encoded with payloads that can eat through either 0:22:18.716 --> 0:22:23.716 the biofilms, mucle layers or macrophage layers that protect those 0:22:23.716 --> 0:22:27.156 intracellular pathogens that our drugs would be able to get 0:22:27.156 --> 0:22:33.276 there precisely and kill just those pathogens, thereby causing the 0:22:33.276 --> 0:22:37.756 immune system to calm down and to potentially heal that 0:22:37.876 --> 0:22:40.196 patient with something that's curative. 0:22:41.396 --> 0:22:44.076 And just to be clear, is it the case that 0:22:44.116 --> 0:22:49.116 antibiotics just don't work for the particular the bacteria in 0:22:49.156 --> 0:22:50.516 the setting that you're describing. 0:22:50.916 --> 0:22:55.436 Antibiotics are known to not be able to kill intracellular pathogens. 0:22:55.516 --> 0:22:59.036 They can't transit into the human cells to kill the human. 0:22:58.836 --> 0:23:01.716 Cells, which is why they don't kill us. 0:23:01.876 --> 0:23:06.716 Presumably why antibiotics don't kill us. Yeah, presumably, I mean, 0:23:06.756 --> 0:23:08.236 that's one way to look at it. 0:23:08.276 --> 0:23:13.116 Absolutely, yeah, Yeah, And this is a trial that you're 0:23:13.116 --> 0:23:15.876 hoping you're hoping to sort of start a clinical trial 0:23:15.916 --> 0:23:18.756 based on this hypothesis. You said in the next year 0:23:18.836 --> 0:23:19.636 or so, we hope. 0:23:19.476 --> 0:23:22.276 To, We hope to. We still need to raise fund 0:23:22.356 --> 0:23:23.676 specifically for that one. 0:23:23.956 --> 0:23:26.116 I believe it less the way you say we hope to. 0:23:26.276 --> 0:23:29.156 Yeah, that when you're running a company like this, you 0:23:29.236 --> 0:23:32.156 tend to go where your contracts and partnerships are, and 0:23:32.236 --> 0:23:35.876 right now we have contracts in three of four areas, 0:23:35.916 --> 0:23:38.156 and so of course we're busy working on all three 0:23:38.196 --> 0:23:40.836 of those, and we hope to add the fourth. 0:23:41.196 --> 0:23:44.076 So what's the bigger idea here? Like, we kind of 0:23:44.116 --> 0:23:46.356 went far into the weeds on crumbs, But what is 0:23:46.396 --> 0:23:48.876 the bigger idea for you know, if you're right, like, 0:23:48.956 --> 0:23:51.676 what is the big hope for phaci therapy and whatever 0:23:51.756 --> 0:23:52.676 ten years or something. 0:23:53.356 --> 0:23:57.236 So I'll start high level and go down into that. 0:23:58.236 --> 0:24:02.196 Inflammation in the human body is not good. It causes 0:24:02.316 --> 0:24:07.716 many diseases without question, things like rumtory torte is potentially 0:24:07.836 --> 0:24:13.276 neuro disease is Things related to dementia, Parkinson's, etc. Like 0:24:13.316 --> 0:24:16.556 when inflammation occurs in certain sections of the body, bad 0:24:16.596 --> 0:24:20.956 things happen. Our hope for this platform is that it 0:24:20.996 --> 0:24:24.636 can reach into the human body via precision medicine and 0:24:24.716 --> 0:24:27.636 pull those pathogens or pathobians out. 0:24:28.396 --> 0:24:31.996 Is the underlying hypothesis that this sort of mysterious systemic 0:24:32.076 --> 0:24:35.516 inflammation is caused by particular kinds of bacterial infection. 0:24:36.876 --> 0:24:40.956 Yes, many pathogens that are in the body are bad actors. 0:24:41.156 --> 0:24:45.756 They're non transient, and the immune system is likely attacking 0:24:45.916 --> 0:24:49.356 those non transient bad actors. And so if you have 0:24:49.396 --> 0:24:53.516 a platform that can remove those bad actors, you likely 0:24:53.676 --> 0:24:57.716 also get the benefits of being able to improve the 0:24:57.756 --> 0:25:01.196 health of the human body, and that we believe will 0:25:01.236 --> 0:25:07.316 do things like increase the lives of most people in society. 0:25:07.436 --> 0:25:11.076 Or if you're genetically predisposed to a disease, you may 0:25:11.076 --> 0:25:13.556 be able to prevent the onset of that disease for 0:25:13.636 --> 0:25:17.596 a longer period of time. If you're genetically predisposed to 0:25:17.636 --> 0:25:20.316 a disease, you might be able to lessen the severity 0:25:20.796 --> 0:25:24.076 of that disease on your life. A good example might 0:25:24.116 --> 0:25:28.916 be rheumatory authritis. So if you remove pathogens that either 0:25:28.996 --> 0:25:33.436