1 00:00:15,356 --> 00:00:34,196 Speaker 1: Pushkin. I'm Jacob Goldstein. This is What's your Problem? And 2 00:00:34,236 --> 00:00:37,636 Speaker 1: my guest today is Michael Hufford. He's the co founder 3 00:00:37,676 --> 00:00:41,836 Speaker 1: and CEO of a company called Ligenesis. Michael and his 4 00:00:41,956 --> 00:00:44,636 Speaker 1: colleagues are working on a new kind of medical treatment. 5 00:00:45,116 --> 00:00:47,876 Speaker 1: If it works, it will save lives. And I have 6 00:00:47,916 --> 00:00:49,836 Speaker 1: to say the way the treatment is supposed to work 7 00:00:50,116 --> 00:00:53,836 Speaker 1: is wild. It's for people with end stage liver disease 8 00:00:53,956 --> 00:00:56,916 Speaker 1: who don't qualify for a liver transplant. And what le 9 00:00:57,076 --> 00:01:01,036 Speaker 1: Genesis does is they take healthy liver cells, just cells, 10 00:01:01,556 --> 00:01:04,676 Speaker 1: and they inject those cells into the patient's lymph nodes, 11 00:01:05,156 --> 00:01:08,596 Speaker 1: and then the patient grows one or more little new 12 00:01:08,716 --> 00:01:12,596 Speaker 1: liver in those lymph nodes. This has worked in experiments 13 00:01:12,636 --> 00:01:15,756 Speaker 1: in animals, and now they're trying it in people. In 14 00:01:15,796 --> 00:01:19,196 Speaker 1: our conversation, Michael told me about the science of why 15 00:01:19,236 --> 00:01:21,956 Speaker 1: this might work. He told me what it would mean 16 00:01:21,996 --> 00:01:24,716 Speaker 1: for patients if it does work, and we also talked 17 00:01:24,716 --> 00:01:27,196 Speaker 1: about why it might not work. And then we talked 18 00:01:27,196 --> 00:01:30,796 Speaker 1: a little bit about the future of regenerative medicine more broadly, 19 00:01:31,356 --> 00:01:34,316 Speaker 1: and the possibility of a world where no one dies 20 00:01:34,436 --> 00:01:38,396 Speaker 1: waiting for an organ transplant. But to start Michael told 21 00:01:38,436 --> 00:01:44,676 Speaker 1: me some truly interesting facts about the liver and Greek mythology. 22 00:01:44,756 --> 00:01:47,556 Speaker 2: It is remarkable because it's the only organ in the 23 00:01:47,636 --> 00:01:51,236 Speaker 2: human body that will naturally regenerate. So you can lose 24 00:01:51,316 --> 00:01:54,956 Speaker 2: seventy percent of your liver, and over a course of 25 00:01:55,036 --> 00:01:58,316 Speaker 2: just a few weeks, you will regenerate that liver entirely. 26 00:01:58,556 --> 00:02:02,076 Speaker 2: And that's true only for the liver. And ironically, it's 27 00:02:02,076 --> 00:02:04,316 Speaker 2: something we've known for three thousand years, right the myth 28 00:02:04,356 --> 00:02:07,556 Speaker 2: of Prometheus, if you might remember, the titan that stole 29 00:02:07,716 --> 00:02:09,596 Speaker 2: fire from Zeus and gave it to a man was 30 00:02:09,636 --> 00:02:12,556 Speaker 2: punished by being chained to a rock, and that eagle 31 00:02:12,596 --> 00:02:16,036 Speaker 2: would come every day and eat his liver, and the 32 00:02:16,076 --> 00:02:20,276 Speaker 2: punishment was eternal, because his liver would regenerate, an eagle 33 00:02:20,316 --> 00:02:23,956 Speaker 2: would have more liver to feast on the next day. 34 00:02:24,316 --> 00:02:28,796 Speaker 1: I I was vaguely familiar with the myth of Prometheus, 35 00:02:28,836 --> 00:02:30,996 Speaker 1: but I was not familiar with the fact that the 36 00:02:30,996 --> 00:02:33,556 Speaker 1: liver regenerates itself. I mean, do you infer that the 37 00:02:33,596 --> 00:02:35,396 Speaker 1: Greeks knew that? Yeah? 38 00:02:35,436 --> 00:02:39,916 Speaker 2: Absolutely, I think they did know that. I think probably 39 00:02:39,956 --> 00:02:42,436 Speaker 2: through the experiences in battle and what have you, you 40 00:02:42,476 --> 00:02:45,516 Speaker 2: could they could see that you could sustain a dramatic 41 00:02:45,556 --> 00:02:49,156 Speaker 2: injury to the liver and that, unlike any other organ, 42 00:02:49,196 --> 00:02:51,316 Speaker 2: it would regenerate. But at the same time, it's taken 43 00:02:51,396 --> 00:02:54,476 Speaker 2: us three thousand years to get to the point that 44 00:02:54,596 --> 00:02:56,436 Speaker 2: one we can successfully transplant it. 45 00:02:56,516 --> 00:02:56,636 Speaker 1: Right. 46 00:02:56,716 --> 00:03:00,556 Speaker 2: That was the pioneering work of doctor Tom Starzel. You know, 47 00:03:00,556 --> 00:03:02,756 Speaker 2: he first attempted it in nineteen sixty three, got it 48 00:03:02,796 --> 00:03:06,396 Speaker 2: to work in nineteen sixty seven. It saved tens of 49 00:03:06,436 --> 00:03:10,316 Speaker 2: thousands of patients lives since then, and Nowgenesis is really 50 00:03:10,356 --> 00:03:14,316 Speaker 2: standing on the shoulders of folks like doctor Starzel and 51 00:03:14,396 --> 00:03:17,476 Speaker 2: now trying to regenerate the liver in other places in 52 00:03:17,516 --> 00:03:17,956 Speaker 2: the body. 53 00:03:18,716 --> 00:03:21,236 Speaker 1: Let me ask a nitpicky question before I ask a 54 00:03:21,276 --> 00:03:24,396 Speaker 1: real question. Is the skin an organ? And does the 55 00:03:24,396 --> 00:03:25,676 Speaker 1: skin regenerate itself? 56 00:03:26,996 --> 00:03:29,636 Speaker 2: That's a good that's a good point. The skin has 57 00:03:29,676 --> 00:03:32,916 Speaker 2: some ability to regenerate itself, for sure, And in fact, 58 00:03:32,956 --> 00:03:36,036 Speaker 2: in children, if a small child loses the tip of 59 00:03:36,076 --> 00:03:40,116 Speaker 2: a finger in an accident before the age of seven, 60 00:03:40,236 --> 00:03:43,836 Speaker 2: you can actually regrow the tip of your finger. But 61 00:03:43,916 --> 00:03:47,916 Speaker 2: we lose that that remarkable ability to regenerate as we 62 00:03:47,956 --> 00:03:51,996 Speaker 2: get older, and the only organ that retains that capability 63 00:03:52,676 --> 00:03:53,116 Speaker 2: is the liver. 64 00:03:54,316 --> 00:04:01,276 Speaker 1: So you mentioned liver transplants, incredible life saving technology. Let's 65 00:04:01,316 --> 00:04:06,196 Speaker 1: call it a technology. Why why do we need ligenesis? Like, 66 00:04:06,236 --> 00:04:09,956 Speaker 1: what is the limit of liver transplants? Liver transplants? 67 00:04:10,036 --> 00:04:12,996 Speaker 2: We have about nine thousand patients on the US currently 68 00:04:13,516 --> 00:04:17,236 Speaker 2: for a liver transplant. Fifteen to twenty percent of those 69 00:04:17,236 --> 00:04:20,716 Speaker 2: patients will die each year awaiting a liver transplant to 70 00:04:20,756 --> 00:04:24,196 Speaker 2: become available. So I would say it's there's really a 71 00:04:24,396 --> 00:04:27,956 Speaker 2: fundamentally a two fold problem. One is supply and demand. Today, 72 00:04:28,516 --> 00:04:34,156 Speaker 2: one donated organ treats one patient using our technology, a 73 00:04:34,196 --> 00:04:38,156 Speaker 2: single donated organ, because we're isolating the individual liver cells 74 00:04:38,236 --> 00:04:41,596 Speaker 2: or hepatosites from that liver, a single donated organ could 75 00:04:41,596 --> 00:04:46,156 Speaker 2: treat fifty patients. So one, we're kind of fixing and 76 00:04:46,196 --> 00:04:48,836 Speaker 2: really up ending the supply demand calculus when it comes 77 00:04:48,916 --> 00:04:51,436 Speaker 2: to you know, instead of one donated organ treating one patient, 78 00:04:51,836 --> 00:04:54,036 Speaker 2: with our approach, one donated organ can treat up to 79 00:04:54,076 --> 00:04:57,956 Speaker 2: fifty patients. But the other problem is is what oftentimes 80 00:04:57,956 --> 00:05:01,116 Speaker 2: people aren't aware of, which is for all the you know, 81 00:05:01,156 --> 00:05:04,396 Speaker 2: the understandable human drama of a liver transplant weightlist, of 82 00:05:04,836 --> 00:05:07,836 Speaker 2: all the organ transplant weight lists, where people are waiting 83 00:05:07,876 --> 00:05:12,956 Speaker 2: for this life save even gift of organ donation. Many 84 00:05:13,036 --> 00:05:16,196 Speaker 2: patients are too ill to even make the list. So 85 00:05:16,396 --> 00:05:19,556 Speaker 2: in the US you have about five million cases of 86 00:05:19,596 --> 00:05:22,236 Speaker 2: in stage liver disease in one form or another. You 87 00:05:22,276 --> 00:05:27,076 Speaker 2: have eighty five thousand deaths. At least fifty percent of 88 00:05:27,116 --> 00:05:30,036 Speaker 2: the patients that could benefit from an organ transplant don't 89 00:05:30,116 --> 00:05:34,316 Speaker 2: qualify because we know that they simply won't survive the procedure. 90 00:05:34,476 --> 00:05:37,956 Speaker 1: Because it's a big, open surgery that involves a lot 91 00:05:37,956 --> 00:05:40,756 Speaker 1: of trauma, and if you're very sick already, you'll probably 92 00:05:40,796 --> 00:05:43,916 Speaker 1: die from the surgery. Yes. Correct, So you co founded 93 00:05:44,156 --> 00:05:48,516 Speaker 1: the company with scientists with a researcher named Eric Leagas right, 94 00:05:48,516 --> 00:05:51,556 Speaker 1: and it was based on research that he had done. 95 00:05:51,756 --> 00:05:55,956 Speaker 1: So tell me about meeting him where you were and 96 00:05:56,356 --> 00:05:58,356 Speaker 1: what was the work he had done that you found 97 00:05:58,356 --> 00:06:00,276 Speaker 1: so compelling that you had to go start a company 98 00:06:00,316 --> 00:06:01,996 Speaker 1: with him? Yeah, absolutely so. 99 00:06:02,116 --> 00:06:05,796 Speaker 2: Eric Legass is a professor at the McGowan Institute for 100 00:06:05,836 --> 00:06:08,876 Speaker 2: a Generative Medicine and Pathology at the University of Pittsburgh. 101 00:06:09,276 --> 00:06:11,756 Speaker 2: At the time, I was an entrepreneur in residence at 102 00:06:11,796 --> 00:06:14,356 Speaker 2: the University of Pittsburgh and I had spent twenty five 103 00:06:14,396 --> 00:06:16,916 Speaker 2: years doing drug development and had been fortunate to work 104 00:06:16,956 --> 00:06:20,156 Speaker 2: on a number of very innovative programs and had started 105 00:06:20,276 --> 00:06:22,836 Speaker 2: and sold a number of companies. And so was working 106 00:06:22,836 --> 00:06:25,076 Speaker 2: with the University of Pittsburgh because they get almost a 107 00:06:25,116 --> 00:06:31,196 Speaker 2: billion dollars of NIH funding annually. It's remarkably remarkable research enterprise, 108 00:06:31,276 --> 00:06:33,436 Speaker 2: both at the University of Pittsburgh and the University of 109 00:06:33,436 --> 00:06:37,036 Speaker 2: Pittsburgh Medical Center or UPMC, and so they wanted to 110 00:06:37,036 --> 00:06:40,716 Speaker 2: get more companies spun out as a function of that funding. 111 00:06:41,116 --> 00:06:42,716 Speaker 2: And so one day a colleague of mine took me 112 00:06:42,756 --> 00:06:46,476 Speaker 2: to meet Eric Lagas, and what Eric told me was 113 00:06:46,716 --> 00:06:49,876 Speaker 2: a remarkable story in two ways. One, he showed me 114 00:06:49,876 --> 00:06:54,276 Speaker 2: these remarkable pictures from his publication in Nature Biotechnology, showing 115 00:06:54,316 --> 00:06:58,676 Speaker 2: that he could regrow organs in the lymph nodes of mice. 116 00:06:59,356 --> 00:07:02,116 Speaker 2: That he could take liver cells from a mouse and 117 00:07:02,236 --> 00:07:06,596 Speaker 2: graph them into the lymph node of another mouse. And 118 00:07:06,876 --> 00:07:11,476 Speaker 2: these animals had a genetic liver disease, and so as 119 00:07:11,556 --> 00:07:13,956 Speaker 2: a function of that liver disease, they would otherwise die 120 00:07:13,996 --> 00:07:17,076 Speaker 2: from that liver disease. But when he ingrafted these hepatosites 121 00:07:17,076 --> 00:07:21,156 Speaker 2: into their lymph nodes, those lymph nodes acted as living bioreactors, 122 00:07:21,196 --> 00:07:25,876 Speaker 2: and they literally grew those animals miniature livers, so that 123 00:07:26,636 --> 00:07:29,556 Speaker 2: instead of dying from their liver disease, one hundred percent 124 00:07:29,556 --> 00:07:32,836 Speaker 2: of them were rescued from that otherwise fatal liver disease. 125 00:07:32,876 --> 00:07:35,716 Speaker 2: So he had these pictures that were truly jaw dropping, 126 00:07:35,876 --> 00:07:39,156 Speaker 2: you know, of these ectopic organs in places in the 127 00:07:39,196 --> 00:07:40,996 Speaker 2: body that they should not otherwise be. 128 00:07:41,956 --> 00:07:44,676 Speaker 1: So I just want to repeat what you just said 129 00:07:44,716 --> 00:07:47,916 Speaker 1: because it is the central extraordinary fact of the thing 130 00:07:47,956 --> 00:07:52,356 Speaker 1: that you are doing. Right. What Leagas did was he 131 00:07:52,436 --> 00:07:56,636 Speaker 1: had put liver cells, just cells, into the lymph nodes 132 00:07:57,556 --> 00:08:01,116 Speaker 1: of these mice that had liver disease, and within the 133 00:08:01,196 --> 00:08:06,076 Speaker 1: lymph node there grew a teeny liver that worked, that 134 00:08:06,196 --> 00:08:08,636 Speaker 1: did what the big liver needed to do, and the 135 00:08:08,676 --> 00:08:14,116 Speaker 1: mice did die. Like why why should that even be true? Yeah, 136 00:08:14,196 --> 00:08:15,516 Speaker 1: So two things. 137 00:08:15,556 --> 00:08:18,916 Speaker 2: One, over time the lymph node disappears, the lymph node 138 00:08:18,916 --> 00:08:22,516 Speaker 2: acts as a temporary bioreactor to get that ectopic organ 139 00:08:22,516 --> 00:08:25,196 Speaker 2: and by ectopic we just mean in a different place 140 00:08:25,316 --> 00:08:28,956 Speaker 2: in the body that ectopic liver to grow. And in fact, 141 00:08:28,996 --> 00:08:31,836 Speaker 2: those ectopic livers and mice could grow to seventy percent 142 00:08:31,916 --> 00:08:33,796 Speaker 2: the size of a normal liver. So he could grow 143 00:08:34,076 --> 00:08:38,156 Speaker 2: really quite large ectopic livers using these lymph nodes. 144 00:08:38,316 --> 00:08:41,196 Speaker 1: And that doesn't mess the mice up. It doesn't like 145 00:08:41,316 --> 00:08:43,876 Speaker 1: mess up their emphatic system or something like that. 146 00:08:44,396 --> 00:08:48,796 Speaker 2: Yeah, So remarkably, we've seen no untoward effects on the 147 00:08:48,796 --> 00:08:51,916 Speaker 2: immune system, now, partly because let's stop and talk about 148 00:08:51,956 --> 00:08:54,396 Speaker 2: lymph nodes for a second, right, So, lymph nodes in 149 00:08:54,436 --> 00:08:56,916 Speaker 2: the human body, we have four hundred and fifty to 150 00:08:57,036 --> 00:09:00,876 Speaker 2: seven hundred lymph nodes spread throughout our body, a majority 151 00:09:00,956 --> 00:09:04,716 Speaker 2: in our gut area, right, and they've helped us as 152 00:09:04,756 --> 00:09:08,276 Speaker 2: a species survive infection, right, because what a what a 153 00:09:08,356 --> 00:09:12,436 Speaker 2: lymph node does, It's its primary evolutionary function is help 154 00:09:12,516 --> 00:09:16,236 Speaker 2: bioreact T cells. So when you develop a cold, you 155 00:09:16,276 --> 00:09:19,356 Speaker 2: have a sore throat and you feel that nodule that 156 00:09:19,476 --> 00:09:21,676 Speaker 2: kind of you know marble or maybe even you know 157 00:09:22,236 --> 00:09:26,316 Speaker 2: large marble underneath your jaw, that's a lymphnode that's bioreacted 158 00:09:26,596 --> 00:09:29,116 Speaker 2: billions of T cells to help you fight that infection. 159 00:09:29,636 --> 00:09:33,476 Speaker 1: When you say bioreact, you basically mean grow, right, it. 160 00:09:33,396 --> 00:09:38,356 Speaker 2: Is it is an admittedly biotech jargon term for grow. 161 00:09:38,436 --> 00:09:41,316 Speaker 1: That's exactly right. Okay, So the lymph note is a 162 00:09:41,356 --> 00:09:44,556 Speaker 1: really good place for cells to grow. That's one reason 163 00:09:44,636 --> 00:09:47,276 Speaker 1: it works, or it works in animals. You said there 164 00:09:47,276 --> 00:09:49,756 Speaker 1: were two reasons. The what's the other reason? 165 00:09:50,156 --> 00:09:54,116 Speaker 2: The other is what's special about the liver and why 166 00:09:54,676 --> 00:09:57,436 Speaker 2: even the Greeks, you know, knew that it would regenerate 167 00:09:57,556 --> 00:10:02,076 Speaker 2: under the right circumstances. Is the fundamental cell of the 168 00:10:02,116 --> 00:10:06,956 Speaker 2: liver is the hepatocite. Hepatasites are naturally regenerative, and so 169 00:10:07,676 --> 00:10:11,356 Speaker 2: Eric's fundamental s scientific discovery was that if you combine 170 00:10:12,196 --> 00:10:16,876 Speaker 2: that natural regenerative potential of the hapatosite with the natural 171 00:10:16,916 --> 00:10:22,516 Speaker 2: ability of the lymph node to bioreact cells, you get 172 00:10:22,556 --> 00:10:24,796 Speaker 2: this remarkable effect. And you could think of it as 173 00:10:24,836 --> 00:10:27,196 Speaker 2: the flip side of the cancer coin. You know, many 174 00:10:27,196 --> 00:10:31,556 Speaker 2: people are aware that cancer probes the environment to form tumors, 175 00:10:32,316 --> 00:10:37,076 Speaker 2: and very often cancer will grow tumors in someone's lymph nodes. 176 00:10:37,636 --> 00:10:39,836 Speaker 1: Right, And in fact, that the classic sort of staging 177 00:10:39,956 --> 00:10:43,756 Speaker 1: question in cancer set has it spread to the lymph nodes? 178 00:10:43,796 --> 00:10:45,956 Speaker 1: And if it has in the case of cancer, that 179 00:10:46,116 --> 00:10:46,876 Speaker 1: is bad. 180 00:10:47,236 --> 00:10:50,476 Speaker 2: That is bad, exactly right, precisely because lymph nodes are 181 00:10:50,596 --> 00:10:54,276 Speaker 2: such effective bioreactors, and they are agnostic as to what 182 00:10:54,316 --> 00:10:58,276 Speaker 2: they bioreact You know, they're so good at growing cells. Yeah, 183 00:10:58,476 --> 00:11:01,236 Speaker 2: exactly right. So if a cancer cell gets in there, 184 00:11:01,476 --> 00:11:03,916 Speaker 2: the cancer cell thinks, man, that's a fantastic place. I 185 00:11:03,956 --> 00:11:06,636 Speaker 2: have access to blood and nutrients, and I have a 186 00:11:06,676 --> 00:11:10,236 Speaker 2: confined space that I can focus on growth. And what 187 00:11:10,276 --> 00:11:14,156 Speaker 2: you end up are these is the spread of these tumors. Well, 188 00:11:14,316 --> 00:11:18,556 Speaker 2: what Eric realized is that you could turn that biology 189 00:11:18,596 --> 00:11:21,836 Speaker 2: to it to a therapeutic instead of a malignant potential. 190 00:11:22,596 --> 00:11:26,396 Speaker 2: So by putting a self therapy like apatasite into a 191 00:11:26,476 --> 00:11:31,356 Speaker 2: lymph node, you could generate functional tissues that exerted life 192 00:11:31,396 --> 00:11:35,636 Speaker 2: saving effects. And so he showed me those first pictures 193 00:11:35,676 --> 00:11:37,916 Speaker 2: from his study, and it really was jaw dropping. And 194 00:11:37,956 --> 00:11:40,836 Speaker 2: I asked him that afternoon what I thought was the 195 00:11:40,876 --> 00:11:45,076 Speaker 2: gotcha question, because it so often is with academic minded professors. 196 00:11:45,076 --> 00:11:48,196 Speaker 2: I said, well, you know, that's great, Eric, it's incredibly impressive. 197 00:11:48,636 --> 00:11:50,316 Speaker 2: What about large animals. 198 00:11:49,956 --> 00:11:52,956 Speaker 1: Right, it's good news for mice. Right, you must exactly 199 00:11:53,276 --> 00:11:58,156 Speaker 1: the phrase mice lie and primates exaggerate drug. I love 200 00:11:58,236 --> 00:12:01,236 Speaker 1: that I had not heard that. Somebody told me that 201 00:12:01,476 --> 00:12:05,316 Speaker 1: twenty five years that's fantastic. I'm going to steal it. Actually, 202 00:12:05,396 --> 00:12:06,036 Speaker 1: that's wonderful. 203 00:12:06,876 --> 00:12:10,356 Speaker 2: So and he said, oh yeah, Michael. And in fact, 204 00:12:10,396 --> 00:12:14,156 Speaker 2: his colleague, doctor Palofontes, who was our co founder and 205 00:12:14,196 --> 00:12:17,596 Speaker 2: chief medical officer, showed that the exact same principle applied 206 00:12:17,596 --> 00:12:20,116 Speaker 2: in pigs. So they showed you could take a pig 207 00:12:20,156 --> 00:12:23,236 Speaker 2: that would otherwise die from a fatal liver disease, and 208 00:12:23,276 --> 00:12:27,236 Speaker 2: you could rescue that pig using the exact same procedure. 209 00:12:27,356 --> 00:12:30,436 Speaker 2: And they even tried a different model where they surgically 210 00:12:30,476 --> 00:12:33,556 Speaker 2: injure the liver. There's something called a portocable shunt where 211 00:12:33,556 --> 00:12:36,716 Speaker 2: you can go in and kind of rearrange the plumbing 212 00:12:36,756 --> 00:12:39,556 Speaker 2: of the liver, so to speak, to deprivate of blood flow, 213 00:12:40,156 --> 00:12:42,956 Speaker 2: which was a procedure that doctor Starzeal had pioneered as 214 00:12:42,956 --> 00:12:45,756 Speaker 2: a way to test and develop the procedure that would 215 00:12:45,756 --> 00:12:50,396 Speaker 2: eventually become liver transplantation. And again rescued those animals. And 216 00:12:50,436 --> 00:12:52,996 Speaker 2: he told me something that as a drug developer you 217 00:12:53,156 --> 00:12:55,796 Speaker 2: virtually never hear. He said, Michael, I can't get this 218 00:12:55,956 --> 00:12:59,876 Speaker 2: not to work. And as a drug developer, right, I'd 219 00:12:59,876 --> 00:13:02,756 Speaker 2: spent my entire career and the entire industry really is 220 00:13:02,796 --> 00:13:06,676 Speaker 2: focused on getting the exact right drug delivered in the 221 00:13:06,716 --> 00:13:10,156 Speaker 2: exact right way to the exact right patient, exact right dose, 222 00:13:10,836 --> 00:13:13,516 Speaker 2: oftentimes at the exact right time of day, and you 223 00:13:13,596 --> 00:13:16,636 Speaker 2: hope for an effect. And what Eric was telling me 224 00:13:16,836 --> 00:13:20,316 Speaker 2: was that nature had kind of primed this approach between 225 00:13:20,836 --> 00:13:25,636 Speaker 2: the natural originative capacity of the liver the natural bioreactor 226 00:13:25,756 --> 00:13:28,876 Speaker 2: capabilities of the lymph node, and that when he said 227 00:13:28,916 --> 00:13:30,796 Speaker 2: he couldn't get it not to work. Quite literally, the 228 00:13:30,796 --> 00:13:33,036 Speaker 2: hairs on the back of my neck stood up, and 229 00:13:33,116 --> 00:13:34,796 Speaker 2: I said, Okay, let's back up and go over this 230 00:13:34,836 --> 00:13:39,636 Speaker 2: whole story again, you know, And really that day was 231 00:13:39,676 --> 00:13:41,836 Speaker 2: the genesis of the company. 232 00:13:42,756 --> 00:13:47,156 Speaker 1: So you start the company nine years ago, is that right? 233 00:13:47,196 --> 00:13:48,036 Speaker 1: Twenty seventeen? 234 00:13:49,116 --> 00:13:50,396 Speaker 2: Yeah, Yeah, time's flown. 235 00:13:50,436 --> 00:13:53,196 Speaker 1: Yeah yeah. I mean it takes a long time to 236 00:13:53,356 --> 00:13:58,996 Speaker 1: develop new therapies, right, This is regenerative medicine, cell therapy, 237 00:13:59,036 --> 00:14:01,996 Speaker 1: a hard new thing to do. So where are you 238 00:14:02,116 --> 00:14:04,236 Speaker 1: now nine years later? Yeah? 239 00:14:04,276 --> 00:14:07,876 Speaker 2: So we are now running a first in human phase 240 00:14:07,916 --> 00:14:11,156 Speaker 2: two a clinical trial. So this is a clinical trial 241 00:14:11,196 --> 00:14:15,516 Speaker 2: in patients within stage liver disease. These are patients, most 242 00:14:15,556 --> 00:14:18,516 Speaker 2: of them, not all, Most are on the liver transplant 243 00:14:18,516 --> 00:14:22,556 Speaker 2: wait list and they can come into the trial. They 244 00:14:22,596 --> 00:14:25,836 Speaker 2: may have any number of different types of liver disease, 245 00:14:25,916 --> 00:14:29,476 Speaker 2: but we're going for patients who have in stage liver 246 00:14:29,516 --> 00:14:33,236 Speaker 2: disease that typically have a life expectancy of many months 247 00:14:33,276 --> 00:14:36,836 Speaker 2: or a few years, okay, because we know that. We 248 00:14:36,876 --> 00:14:39,196 Speaker 2: know that one limitation of our approach is that when 249 00:14:39,196 --> 00:14:42,676 Speaker 2: you ingraph these cells, they do take time to organize themselves. 250 00:14:42,676 --> 00:14:45,476 Speaker 2: It's not like the next day you have, you know, 251 00:14:46,196 --> 00:14:48,916 Speaker 2: a fully functioning actopic liver. We know that it takes 252 00:14:48,956 --> 00:14:51,956 Speaker 2: probably two to three months, is our best guess, and 253 00:14:51,996 --> 00:14:54,596 Speaker 2: so we want to make sure that these patients have 254 00:14:54,716 --> 00:14:59,356 Speaker 2: the time to have the potential beneficial effects of the therapy. 255 00:14:59,436 --> 00:15:02,116 Speaker 2: So we've now transplanted our first cohort of patients. There 256 00:15:02,116 --> 00:15:06,596 Speaker 2: were four patients, all done at the Houston Methodist Hospital. 257 00:15:07,116 --> 00:15:10,276 Speaker 2: Like you typically the phrases, you start low and go slow, 258 00:15:10,356 --> 00:15:12,796 Speaker 2: you start low in dose and go slow because you're 259 00:15:12,836 --> 00:15:15,356 Speaker 2: not sure what the effect will be. And so the 260 00:15:15,436 --> 00:15:18,556 Speaker 2: FDA had counseled us this first trial is just going 261 00:15:18,596 --> 00:15:22,596 Speaker 2: to be twelve patients, so we have three different dose groups. 262 00:15:23,396 --> 00:15:26,116 Speaker 2: We've completed that first dose cohort and we had a 263 00:15:26,196 --> 00:15:28,756 Speaker 2: data Safety Monitoring Board meeting where they look at all 264 00:15:28,796 --> 00:15:31,796 Speaker 2: the safety data and the efficacy data to date and 265 00:15:31,836 --> 00:15:33,916 Speaker 2: they said, okay, you know, it's looking good. Let's let's 266 00:15:33,996 --> 00:15:37,436 Speaker 2: go on and dose escalate as per the protocol. And 267 00:15:37,516 --> 00:15:40,076 Speaker 2: so that's that's what we are in the midst of 268 00:15:40,196 --> 00:15:40,636 Speaker 2: right now. 269 00:15:41,556 --> 00:15:45,436 Speaker 1: One are you going to know if it worked, if 270 00:15:45,476 --> 00:15:48,276 Speaker 1: this trial, you know, had a positive result, that will 271 00:15:48,356 --> 00:15:51,916 Speaker 1: allow you to move to presumably the next bigger trial. 272 00:15:52,556 --> 00:15:54,396 Speaker 2: Yeah, we should have a very good sense of that 273 00:15:54,476 --> 00:15:56,796 Speaker 2: in the middle part of next year. Okay, so the 274 00:15:56,836 --> 00:15:59,636 Speaker 2: middle part of twenty twenty seven, and then yeah, move 275 00:15:59,676 --> 00:16:00,196 Speaker 2: on from there. 276 00:16:00,636 --> 00:16:03,716 Speaker 1: So let's talk about how it works. So there's a patient, 277 00:16:03,836 --> 00:16:08,596 Speaker 1: as you've said, yeah, who is you know, has liver disease, 278 00:16:09,236 --> 00:16:11,916 Speaker 1: has some liver function left, but it's not looking good 279 00:16:11,916 --> 00:16:14,916 Speaker 1: for them. And then there is what a donated liver. 280 00:16:15,076 --> 00:16:16,996 Speaker 1: Like what actually happens. 281 00:16:17,236 --> 00:16:20,436 Speaker 2: That's exactly right. When an organ becomes available, if the 282 00:16:20,516 --> 00:16:24,596 Speaker 2: organ is eligible for transplant, then it's transplanted into a 283 00:16:24,636 --> 00:16:28,636 Speaker 2: patient that needs it. Some organs, though, are not eligible 284 00:16:28,676 --> 00:16:31,676 Speaker 2: for transplant, and that can be for any number of reasons. 285 00:16:31,716 --> 00:16:35,196 Speaker 2: They may have been injured because of the cause of death, 286 00:16:36,036 --> 00:16:39,116 Speaker 2: they might be a little fatty where when the transplant 287 00:16:39,196 --> 00:16:41,796 Speaker 2: surgeon looks at the organ they think, ah, you know, 288 00:16:41,836 --> 00:16:44,836 Speaker 2: that's not going to be a great fit for this 289 00:16:44,876 --> 00:16:48,116 Speaker 2: particular patient, and so that they pass on it when 290 00:16:48,196 --> 00:16:51,756 Speaker 2: they come to us. We then have a facility at 291 00:16:51,796 --> 00:16:55,676 Speaker 2: Houston Methodist currently where we can take that organ and 292 00:16:55,716 --> 00:16:59,676 Speaker 2: it takes us just about four or five hours. It's 293 00:16:59,676 --> 00:17:03,156 Speaker 2: a seventy plus step process, but we start with the 294 00:17:03,156 --> 00:17:07,116 Speaker 2: full organ and after seventy steps and about four to 295 00:17:07,196 --> 00:17:11,556 Speaker 2: five hours, we've isolated and suspended those hepatocytes into a 296 00:17:11,596 --> 00:17:17,716 Speaker 2: solution that we then currier over to the endoscopic ultrasound suite. 297 00:17:18,476 --> 00:17:21,756 Speaker 1: And so just to be clear, it's it's when you 298 00:17:21,756 --> 00:17:24,716 Speaker 1: say the patasites are in a solution, it's like a 299 00:17:24,796 --> 00:17:27,236 Speaker 1: bottle full of liver cells in liquid. 300 00:17:27,556 --> 00:17:30,796 Speaker 2: That's That's That's exactly what it is. Okay, It's a 301 00:17:30,796 --> 00:17:34,396 Speaker 2: small syringe really because really injecting about yeah, about one 302 00:17:34,996 --> 00:17:38,436 Speaker 2: about one milliliter of the cell suspension. But it's it's 303 00:17:38,476 --> 00:17:42,396 Speaker 2: literally like a brown thick liquid. 304 00:17:42,476 --> 00:17:44,916 Speaker 1: That's yeah, So a syringe like like what like you'd 305 00:17:44,916 --> 00:17:47,076 Speaker 1: get in a shot, but instead of a vaccine, it's 306 00:17:47,276 --> 00:17:49,716 Speaker 1: liver cells from a donated liver. Okay, so then you 307 00:17:49,796 --> 00:17:52,516 Speaker 1: cur youer that over to go go on. Yeah. 308 00:17:52,756 --> 00:17:54,956 Speaker 2: Yeah, And so the patient is put under light sedation 309 00:17:55,716 --> 00:17:58,596 Speaker 2: and just the way you might have an endoscope you know, 310 00:17:58,676 --> 00:18:00,596 Speaker 2: to look to see if you have an ulcer or 311 00:18:00,676 --> 00:18:04,596 Speaker 2: to you know, have any number of diagnostic procedures. Yes, Basically, 312 00:18:04,596 --> 00:18:08,876 Speaker 2: an endoscopius takes that into scope under sedation, down through 313 00:18:08,916 --> 00:18:12,956 Speaker 2: the mouth of the patient and then threads it down 314 00:18:12,996 --> 00:18:16,556 Speaker 2: their gi track kind of into their gut area. And 315 00:18:16,636 --> 00:18:20,316 Speaker 2: at the end of that endoscope is an ultrasound. And 316 00:18:20,356 --> 00:18:24,636 Speaker 2: so the ultrasound you can basically look adjacent to the 317 00:18:24,676 --> 00:18:28,596 Speaker 2: gut wall and lymph nodes there show up. Is they 318 00:18:28,596 --> 00:18:31,396 Speaker 2: almost look like bubbles to the untrained eye, right, So 319 00:18:32,236 --> 00:18:35,036 Speaker 2: they kind of look like these bubbles that come into 320 00:18:35,116 --> 00:18:40,156 Speaker 2: view via the ultrasound, and the endoscopist takes a five 321 00:18:40,196 --> 00:18:44,836 Speaker 2: foot needle that threads down through the industry thing. Yeah, 322 00:18:44,916 --> 00:18:48,716 Speaker 2: it then goes through the gut wall and punctures into 323 00:18:48,756 --> 00:18:49,516 Speaker 2: the lymph node. 324 00:18:50,796 --> 00:18:52,836 Speaker 1: So it's like a shot. It's like a shot, but 325 00:18:52,876 --> 00:18:57,116 Speaker 1: it's going into your stomach, across the wall of your 326 00:18:57,116 --> 00:18:59,996 Speaker 1: stomach and into the lymph node. That's exactly right. That's 327 00:19:00,036 --> 00:19:00,676 Speaker 1: exactly right. 328 00:19:00,716 --> 00:19:03,636 Speaker 2: And so this takes about ten minutes to find the 329 00:19:03,716 --> 00:19:06,996 Speaker 2: lymph node and inject the cell suspension. And so we 330 00:19:07,036 --> 00:19:11,716 Speaker 2: inject one millileter to that lymph node. They withdraw the 331 00:19:11,756 --> 00:19:15,676 Speaker 2: needle and pull the scope out, and the procedure itself 332 00:19:15,716 --> 00:19:17,796 Speaker 2: at that point is done. The cells are in the 333 00:19:17,876 --> 00:19:21,716 Speaker 2: lymph node. The patients put on immune suppression. 334 00:19:21,836 --> 00:19:24,796 Speaker 1: Right, the patients put on immune suppression because these are 335 00:19:24,916 --> 00:19:26,556 Speaker 1: cells from somebody else. So it's just like if you 336 00:19:26,596 --> 00:19:29,596 Speaker 1: get a transplant, your body's cells will be like, oh, 337 00:19:29,676 --> 00:19:32,076 Speaker 1: that's foreign, I'm going to get rid of it. That's 338 00:19:32,156 --> 00:19:34,316 Speaker 1: exactly right. Yeah, okay, So the patients put on immune 339 00:19:34,316 --> 00:19:38,116 Speaker 1: suppression and then if it works, what happens. 340 00:19:39,396 --> 00:19:43,516 Speaker 2: If it works, what happens is those cells find themselves 341 00:19:43,516 --> 00:19:47,916 Speaker 2: in an environment that they find very comforting and very nourishing, 342 00:19:48,036 --> 00:19:53,156 Speaker 2: and so they use that those bioreactor, you know, aspects 343 00:19:53,196 --> 00:19:57,076 Speaker 2: of the lymph node begin dividing because they're natural stem cells, 344 00:19:57,116 --> 00:20:00,956 Speaker 2: and they begin organizing themselves into liveral obdules, which are 345 00:20:00,996 --> 00:20:04,276 Speaker 2: these little hexagonal collections of cells that are kind of 346 00:20:04,276 --> 00:20:09,516 Speaker 2: the functioning filtering unit of the liver. And from all 347 00:20:09,556 --> 00:20:12,156 Speaker 2: of our preclinical data in both small and large animals, 348 00:20:12,756 --> 00:20:16,516 Speaker 2: that division will continue to go on and the vascularization 349 00:20:16,676 --> 00:20:20,716 Speaker 2: will then occur. So the lymph nodes are well vascularized anyway. 350 00:20:20,916 --> 00:20:25,876 Speaker 2: But what you find is that these ectopic organs recruit 351 00:20:27,516 --> 00:20:32,276 Speaker 2: cells from the patient's body to form additional vasculature, so 352 00:20:32,316 --> 00:20:37,756 Speaker 2: additional blood flow to that ectopic organ, so that over time, 353 00:20:38,396 --> 00:20:40,316 Speaker 2: and again our best guess is it's over a few 354 00:20:40,356 --> 00:20:43,476 Speaker 2: months of time, what you'll be left with is this 355 00:20:43,636 --> 00:20:49,236 Speaker 2: functioning ectopic organs. So I'm picturing one like tiny little 356 00:20:49,316 --> 00:20:54,556 Speaker 2: mini liver, like, I don't know how big is it? 357 00:20:54,596 --> 00:20:55,476 Speaker 2: Is there only one? 358 00:20:55,796 --> 00:20:57,596 Speaker 1: How big does it have to be or how many 359 00:20:57,596 --> 00:20:59,796 Speaker 1: do there have to be for it to be clinically useful? 360 00:21:00,516 --> 00:21:03,636 Speaker 2: They can get quite large. In small animals. You can 361 00:21:03,636 --> 00:21:07,196 Speaker 2: get up to seventy percent of the native liver grown 362 00:21:07,356 --> 00:21:09,676 Speaker 2: in a lymph node, and the larger animal was a 363 00:21:09,716 --> 00:21:14,676 Speaker 2: smaller percentage. And your question about clinically meaningful. You know, 364 00:21:15,076 --> 00:21:17,996 Speaker 2: when you talk to hepatologists or folks like our chief 365 00:21:18,036 --> 00:21:21,036 Speaker 2: medical officer, doctor Fontes, who's treated these patients, you know, 366 00:21:21,036 --> 00:21:25,076 Speaker 2: across his entire life, if you can bump the functional 367 00:21:25,236 --> 00:21:27,956 Speaker 2: amount of liver for one of these patients by ten 368 00:21:28,036 --> 00:21:31,676 Speaker 2: to twenty percent, you will alleviate a lot of the 369 00:21:31,716 --> 00:21:34,916 Speaker 2: signs and symptoms of their in stage liver disease. And 370 00:21:34,956 --> 00:21:37,036 Speaker 2: in fact, in stage liver disease is a problem because 371 00:21:37,116 --> 00:21:39,676 Speaker 2: very often patients don't know that they have advanced liver 372 00:21:39,756 --> 00:21:43,876 Speaker 2: disease until pretty far along, because it is a redundant system. 373 00:21:44,196 --> 00:21:46,716 Speaker 2: As a species, we have very large livers to help us, 374 00:21:46,716 --> 00:21:48,356 Speaker 2: you know, with the various things that we might eat 375 00:21:48,396 --> 00:21:51,476 Speaker 2: and get exposed to. So it's a redundant system and 376 00:21:51,516 --> 00:21:53,596 Speaker 2: by the time you know you have a problem, you 377 00:21:53,636 --> 00:21:57,276 Speaker 2: know you really have a problem. And so that's why 378 00:21:57,316 --> 00:21:58,996 Speaker 2: we think if we can even bump it up by 379 00:21:59,076 --> 00:22:01,716 Speaker 2: ten to twenty percent, I think this will be a 380 00:22:01,796 --> 00:22:07,276 Speaker 2: transformative therapy. So, you know, we envision clinically the potential 381 00:22:07,316 --> 00:22:09,796 Speaker 2: both to treat patients that are never going to get 382 00:22:09,796 --> 00:22:12,036 Speaker 2: an organ because they simply don't qualify for the list, 383 00:22:12,596 --> 00:22:15,756 Speaker 2: but for others it may be more clinically, what you're 384 00:22:15,756 --> 00:22:18,356 Speaker 2: doing is just buying them time so that an organ 385 00:22:18,476 --> 00:22:19,236 Speaker 2: can become. 386 00:22:19,036 --> 00:22:25,996 Speaker 1: Available for them. We're gonna take an ad break right now, 387 00:22:26,276 --> 00:22:27,996 Speaker 1: and then we're gonna come back and talk about a 388 00:22:27,996 --> 00:22:30,876 Speaker 1: bunch of more things, including why what Michael, and like 389 00:22:30,996 --> 00:22:41,996 Speaker 1: genesis are working on might not work. I want to 390 00:22:41,996 --> 00:22:46,236 Speaker 1: go back to one detail or one step you mentioned 391 00:22:46,356 --> 00:22:50,236 Speaker 1: of what happens inside the body in this process, and 392 00:22:50,276 --> 00:22:54,116 Speaker 1: that is, after the cells have been injected, they are 393 00:22:54,236 --> 00:22:58,636 Speaker 1: just cells. They're just random liver cells floating around. And 394 00:22:58,676 --> 00:23:02,996 Speaker 1: you said they organize themselves essentially into a liver, into 395 00:23:03,036 --> 00:23:04,556 Speaker 1: a little liver. You didn't say into a living over 396 00:23:04,676 --> 00:23:08,516 Speaker 1: but that is essentially what's happening. Yeah, that part that 397 00:23:08,596 --> 00:23:13,036 Speaker 1: seems like the central shocking thing that is going on here, right, 398 00:23:13,196 --> 00:23:16,756 Speaker 1: And I've talked to a couple of other people doing 399 00:23:17,356 --> 00:23:23,116 Speaker 1: regenerative medicine in other way, somebody doing bones, somebody doing 400 00:23:23,116 --> 00:23:27,156 Speaker 1: blood vessels, and they both use this term that I 401 00:23:27,236 --> 00:23:29,276 Speaker 1: think I've seen you use elsewhere and that I'm reminded 402 00:23:29,316 --> 00:23:32,436 Speaker 1: of here, and that is it's more of a phrase 403 00:23:32,556 --> 00:23:37,116 Speaker 1: that is that cells are intelligent. Cells have some intelligence, 404 00:23:37,196 --> 00:23:41,916 Speaker 1: which is not intuitive, but but I'm reminded of it here. 405 00:23:41,956 --> 00:23:44,116 Speaker 1: Like what's going on? How does that work? 406 00:23:44,636 --> 00:23:47,316 Speaker 2: It's a great question, and in fact, it's almost a 407 00:23:47,396 --> 00:23:51,556 Speaker 2: testimony to why lie genesis exists. That many academic researches 408 00:23:51,596 --> 00:23:55,676 Speaker 2: that never found companies can get not distracted because it's 409 00:23:55,676 --> 00:23:59,596 Speaker 2: really the fundamental scientific pursuit of why and how. But 410 00:23:59,756 --> 00:24:01,436 Speaker 2: to Eric's credit, when he's. 411 00:24:01,436 --> 00:24:03,916 Speaker 1: So long you don't know the answer, you don't. 412 00:24:03,716 --> 00:24:09,196 Speaker 2: Know, You're absolutely right. The short answer is we don't know. 413 00:24:09,316 --> 00:24:14,116 Speaker 2: The longer answer is yeah, well, short answers we don't 414 00:24:14,116 --> 00:24:18,956 Speaker 2: know too. I think you're right. The cells are remarkably intelligent, 415 00:24:19,076 --> 00:24:21,716 Speaker 2: and we know there's those dozens of pro growth signals 416 00:24:21,756 --> 00:24:24,836 Speaker 2: from the disease liver. We know they play a role, 417 00:24:25,156 --> 00:24:28,716 Speaker 2: but exactly how it works, I'm thankful. Let's put it 418 00:24:28,716 --> 00:24:31,596 Speaker 2: this way that Eric focused on trying to get it 419 00:24:31,636 --> 00:24:33,956 Speaker 2: not to work, because he ended up finding that it 420 00:24:33,996 --> 00:24:37,036 Speaker 2: was so robust, where you know, a lot of researchers 421 00:24:37,036 --> 00:24:39,396 Speaker 2: would been their whole life trying to understand the why 422 00:24:39,436 --> 00:24:40,476 Speaker 2: and how well. 423 00:24:40,316 --> 00:24:45,036 Speaker 1: And clearly in other organs or body parts, like I 424 00:24:45,076 --> 00:24:47,956 Speaker 1: remember in the case of blood vessels, and this is 425 00:24:48,156 --> 00:24:52,716 Speaker 1: a classic challenge when people are trying to grow organs 426 00:24:52,756 --> 00:24:55,276 Speaker 1: or mini organs, is they do a lot of work 427 00:24:55,316 --> 00:24:58,436 Speaker 1: to create the scaffolding, to create the structure, right, and 428 00:24:58,516 --> 00:25:01,996 Speaker 1: so the fact that in this instance it is naturally 429 00:25:02,036 --> 00:25:06,556 Speaker 1: self organizing solves what seems to be the largest problem 430 00:25:06,676 --> 00:25:08,796 Speaker 1: or at least a key problem. 431 00:25:08,836 --> 00:25:12,796 Speaker 2: For any other organs, I would just say, yeah, it 432 00:25:12,836 --> 00:25:15,556 Speaker 2: is better to be lucky than good, and that really 433 00:25:15,636 --> 00:25:20,956 Speaker 2: is a case. Nature has really engineered this in a 434 00:25:20,996 --> 00:25:24,516 Speaker 2: lot of respects. Right As a drug developer, so often 435 00:25:24,556 --> 00:25:27,116 Speaker 2: you're trying to trick the body, right, like you're trying 436 00:25:27,116 --> 00:25:30,236 Speaker 2: to trick it to do something that's unnatural and have 437 00:25:30,316 --> 00:25:32,916 Speaker 2: to fight against it all along the way. I think 438 00:25:32,956 --> 00:25:36,276 Speaker 2: what excites me about regenerative medicine, but like genesis in particular, 439 00:25:36,396 --> 00:25:38,396 Speaker 2: is that we just have a lot of headwinds because 440 00:25:38,876 --> 00:25:44,156 Speaker 2: of evolution and biology than the naturally regenerative capability of 441 00:25:44,196 --> 00:25:47,076 Speaker 2: the liver, the natural ability of the lymph node to 442 00:25:47,116 --> 00:25:49,876 Speaker 2: buy or react a variety of tissues. Because Eric shown 443 00:25:49,916 --> 00:25:53,036 Speaker 2: that it's not just to patasites and ectopic livers, he 444 00:25:53,076 --> 00:25:57,236 Speaker 2: can grow. He can put pancreatic islets and rescue animals 445 00:25:57,236 --> 00:26:00,716 Speaker 2: that have diabetes by putting those islets into lymph nodes. 446 00:26:00,756 --> 00:26:06,476 Speaker 2: He can put the thymus from a young animal into 447 00:26:07,276 --> 00:26:10,836 Speaker 2: the lymph node of an old animal and help reboot 448 00:26:10,876 --> 00:26:13,996 Speaker 2: that old animal's immune system, and in fact the whole 449 00:26:14,036 --> 00:26:18,756 Speaker 2: animal starts to look more youthful physiologically as a function 450 00:26:18,836 --> 00:26:21,876 Speaker 2: of that. So I think the lymph node is going 451 00:26:21,916 --> 00:26:25,396 Speaker 2: to act as a platform for a variety of different tissues, 452 00:26:25,436 --> 00:26:28,916 Speaker 2: and so at like genesis, where the liver is certainly 453 00:26:28,916 --> 00:26:31,916 Speaker 2: the most you know, far along of the assets we have, 454 00:26:31,996 --> 00:26:34,236 Speaker 2: but we also have this work on the thymus and 455 00:26:34,276 --> 00:26:37,116 Speaker 2: the kidney and the pancreas, because as I said, the 456 00:26:37,156 --> 00:26:40,236 Speaker 2: lymph node is it's just remarkably agnostic about the type 457 00:26:40,236 --> 00:26:42,196 Speaker 2: of tissue that it bioreacts. 458 00:26:42,556 --> 00:26:44,556 Speaker 1: And just to be clear that other work that is 459 00:26:45,156 --> 00:26:47,556 Speaker 1: that is not yet in humans, right, that is earlier year. 460 00:26:47,596 --> 00:26:51,076 Speaker 1: That's correct, That's exactly right. Yeah, so correct in the 461 00:26:51,116 --> 00:26:53,196 Speaker 1: liver trial, which is the one that's the farthest along. 462 00:26:53,236 --> 00:26:56,716 Speaker 1: So let's talk about that. What might go wrong? Why 463 00:26:56,756 --> 00:26:57,596 Speaker 1: might it not work? 464 00:26:58,156 --> 00:27:02,996 Speaker 2: In terms of what might go wrong, our body's ability 465 00:27:03,276 --> 00:27:06,796 Speaker 2: to reject what's called allogenetic, which is just the medical 466 00:27:06,876 --> 00:27:10,756 Speaker 2: term right for from another from another person, say, from 467 00:27:10,836 --> 00:27:14,996 Speaker 2: another animal. Our body's ability to do that has been 468 00:27:15,076 --> 00:27:18,116 Speaker 2: central to our success as a species. And as a result, 469 00:27:18,676 --> 00:27:20,956 Speaker 2: when you try to get around it, you have to 470 00:27:21,036 --> 00:27:25,116 Speaker 2: use very powerful drugs to try to convince it not 471 00:27:25,396 --> 00:27:29,236 Speaker 2: to reject those cells. And so I think acute rejection, 472 00:27:29,756 --> 00:27:32,676 Speaker 2: especially when you're injecting a relatively small number of cells 473 00:27:32,676 --> 00:27:35,636 Speaker 2: as compared to a very large organ. I think that's 474 00:27:35,676 --> 00:27:38,076 Speaker 2: one thing that you worry about. 475 00:27:37,996 --> 00:27:40,836 Speaker 1: Oh, the small number of cells, because it's like easier 476 00:27:40,836 --> 00:27:43,396 Speaker 1: for the body with its immune response to wipe out 477 00:27:43,396 --> 00:27:46,876 Speaker 1: a small number of cells. Isn't exactly right? Yeah, dumb question. 478 00:27:48,076 --> 00:27:51,356 Speaker 1: I mean I sort of know the answer. But presumably 479 00:27:51,396 --> 00:27:53,996 Speaker 1: the patients with liver disease have some of their own 480 00:27:54,036 --> 00:27:56,836 Speaker 1: liver cells left. Yes, what if you took some of 481 00:27:56,876 --> 00:27:59,196 Speaker 1: their own liver cells and put them in the lymph node, 482 00:27:59,236 --> 00:28:01,316 Speaker 1: you wouldn't have the rejection problem. 483 00:28:01,716 --> 00:28:03,956 Speaker 2: That's a great question, and we get that a lot 484 00:28:04,916 --> 00:28:07,436 Speaker 2: for the patients that were targeting within stage's liver disease. 485 00:28:07,516 --> 00:28:11,916 Speaker 2: The liver is also grown to potentially catastrophic bleeding risk, 486 00:28:12,916 --> 00:28:17,636 Speaker 2: and so the notion of biopsing a fibrotic liver is 487 00:28:17,716 --> 00:28:21,396 Speaker 2: one that has, you know, very significant medical risks associated 488 00:28:21,436 --> 00:28:21,716 Speaker 2: with it. 489 00:28:21,916 --> 00:28:23,876 Speaker 1: Okay, another one. I'm just good. I'm this one. I'm 490 00:28:23,876 --> 00:28:30,276 Speaker 1: just making up. Can you do like induced pluripotent stem 491 00:28:30,276 --> 00:28:33,076 Speaker 1: cells from the patient and turn them into liver cells. 492 00:28:33,876 --> 00:28:36,476 Speaker 2: That's that is exactly our vision actually for our for 493 00:28:36,516 --> 00:28:39,196 Speaker 2: our second generation therapy. So our first generation therapy is 494 00:28:39,196 --> 00:28:42,076 Speaker 2: going to be these allogenetic cells. The second generation will 495 00:28:42,076 --> 00:28:45,556 Speaker 2: be exactly that, the hope, and there are labs around 496 00:28:45,596 --> 00:28:48,196 Speaker 2: the world working on this. No one's solved it yet. 497 00:28:48,236 --> 00:28:51,396 Speaker 2: But induced pluripotent stem cells where you take a skin 498 00:28:51,476 --> 00:28:54,276 Speaker 2: cell and you push it back to a more embryonic 499 00:28:54,436 --> 00:28:56,796 Speaker 2: like state and then bring it forward as a different 500 00:28:56,796 --> 00:28:59,596 Speaker 2: cell type. You know, we've had tremendous success in a 501 00:28:59,676 --> 00:29:03,516 Speaker 2: variety of cell types to have a fully mature human 502 00:29:03,556 --> 00:29:06,236 Speaker 2: hepatocide is something that no one's been able to do yet. 503 00:29:06,756 --> 00:29:09,356 Speaker 1: Nobody's been able to get a stem cell to turn 504 00:29:09,396 --> 00:29:13,596 Speaker 1: into a mature human liver cell. Oh exactly, So okay, 505 00:29:13,636 --> 00:29:16,436 Speaker 1: So immune rejection that's one problem. What else? 506 00:29:17,276 --> 00:29:20,276 Speaker 2: You know, one thing that we didn't worry a lot about, 507 00:29:20,356 --> 00:29:24,156 Speaker 2: but just because we had endoscopic colleagues that assured us 508 00:29:24,196 --> 00:29:26,476 Speaker 2: this was a very safe procedure. But you know, I've 509 00:29:26,476 --> 00:29:29,236 Speaker 2: taken several drugs first into human you always worry, and 510 00:29:29,316 --> 00:29:32,476 Speaker 2: so with patients with bleeding risk, you know, the the 511 00:29:32,516 --> 00:29:36,116 Speaker 2: indoscopic ultrasound is something that you want to make sure 512 00:29:36,196 --> 00:29:40,196 Speaker 2: goes well. But again we're using incredibly talented endoscopist. They 513 00:29:40,716 --> 00:29:43,716 Speaker 2: do the same procedure to look for patients who've been 514 00:29:43,836 --> 00:29:47,396 Speaker 2: newly diagnosed with pancreatic cancer. The good news is we're 515 00:29:47,436 --> 00:29:51,076 Speaker 2: asking endoscopists to do something they're very familiar with, using 516 00:29:51,116 --> 00:29:53,876 Speaker 2: equipment they're very familiar with. But still you always worry 517 00:29:53,916 --> 00:29:56,316 Speaker 2: about you know, you're going through the gut wall with 518 00:29:56,356 --> 00:29:58,196 Speaker 2: a needle and into a lymph node, and you know 519 00:29:58,236 --> 00:30:00,636 Speaker 2: you always want that to go well. And at this 520 00:30:00,676 --> 00:30:04,756 Speaker 2: point we've had no serious adverse events from the administration itself, 521 00:30:05,476 --> 00:30:07,796 Speaker 2: but that's something you know, that's why you start low 522 00:30:07,836 --> 00:30:09,876 Speaker 2: and go slow, as they say, right in these first 523 00:30:09,876 --> 00:30:10,756 Speaker 2: and human trials. 524 00:30:10,876 --> 00:30:14,956 Speaker 1: And then so these are the sort of technical risks 525 00:30:15,036 --> 00:30:19,276 Speaker 1: or medical risks. Is there like running out of money? 526 00:30:19,316 --> 00:30:22,556 Speaker 1: I mean a biotech company with no product, Like, how's 527 00:30:22,556 --> 00:30:23,716 Speaker 1: how's that part of it? 528 00:30:24,396 --> 00:30:26,276 Speaker 2: Sure? Yeah, there's always business risk. 529 00:30:26,356 --> 00:30:26,516 Speaker 1: You know. 530 00:30:26,676 --> 00:30:28,796 Speaker 2: I was told a long time ago that the the 531 00:30:28,836 --> 00:30:32,236 Speaker 2: definition of a biotech is a company unencumbered with revenues. 532 00:30:33,076 --> 00:30:35,476 Speaker 1: And you know you don't have to worry about the 533 00:30:35,516 --> 00:30:38,356 Speaker 1: profit loss exactly only half. 534 00:30:38,236 --> 00:30:40,196 Speaker 2: You and l is very yeah, we only have half 535 00:30:40,236 --> 00:30:43,116 Speaker 2: of it. So I will say that, Yeah, you always 536 00:30:43,156 --> 00:30:45,876 Speaker 2: worry about running out of money. Drug development always takes 537 00:30:45,916 --> 00:30:48,676 Speaker 2: longer and costs more than you hope it will, even 538 00:30:48,716 --> 00:30:51,476 Speaker 2: when you've done it a long time, there's always surprising challenges. 539 00:30:51,756 --> 00:30:54,916 Speaker 2: I will say, you know, we're fortunate to have wonderful 540 00:30:54,956 --> 00:30:58,356 Speaker 2: investors that are patient with us despite the inevitable setbacks 541 00:30:58,396 --> 00:31:02,316 Speaker 2: as we push forward. As a drug developer, you're always 542 00:31:02,356 --> 00:31:04,756 Speaker 2: taught that great drugs are killed at least three times 543 00:31:04,836 --> 00:31:07,636 Speaker 2: right before they actually make it over the finish line. 544 00:31:07,676 --> 00:31:09,956 Speaker 2: So we have we have folks that are with us 545 00:31:10,036 --> 00:31:12,716 Speaker 2: and supporting us, and we've tried to be very cappully efficient. 546 00:31:12,756 --> 00:31:16,036 Speaker 2: Like Genesis is just half a dozen people. We've raised 547 00:31:16,396 --> 00:31:18,796 Speaker 2: under forty million dollars to date, where when you look 548 00:31:18,796 --> 00:31:21,916 Speaker 2: at the typical cost to get an investigational new drug 549 00:31:21,956 --> 00:31:25,236 Speaker 2: clearance by the FDA or a IP that usually costs 550 00:31:25,316 --> 00:31:27,956 Speaker 2: hundreds of millions of dollars, and just you know, we've 551 00:31:28,276 --> 00:31:32,556 Speaker 2: been fortunate to not need a staggering amount of capital 552 00:31:32,636 --> 00:31:34,956 Speaker 2: to get to where we are, which is in the clinic, 553 00:31:35,356 --> 00:31:38,436 Speaker 2: in part because of the NIH funding that Eric Leagas 554 00:31:38,476 --> 00:31:41,356 Speaker 2: had at the University of Pittsburgh. And it really is 555 00:31:41,396 --> 00:31:44,836 Speaker 2: why the NIH cuts that we've seen happen really are 556 00:31:44,956 --> 00:31:49,036 Speaker 2: undermining the kind of future potential of so many new 557 00:31:49,076 --> 00:31:52,036 Speaker 2: therapies and technologies that you're simply not going to hear 558 00:31:52,076 --> 00:31:55,596 Speaker 2: about because the funding wasn't available for them to move forward. 559 00:31:55,596 --> 00:31:58,836 Speaker 2: But thankfully Eric's work was very well funded by the 560 00:31:58,916 --> 00:32:01,836 Speaker 2: NIH and so we've we've been able to take it forward. 561 00:32:03,236 --> 00:32:05,156 Speaker 1: So I just want to talk for a minute more 562 00:32:05,236 --> 00:32:10,036 Speaker 1: broadly about straight to such should we talk about cellular 563 00:32:10,116 --> 00:32:13,716 Speaker 1: therapy or regenerative medicine? Right, you're kind of both. Yeah, 564 00:32:14,156 --> 00:32:17,836 Speaker 1: we're sort of reading the world, right, but I'm not sure. 565 00:32:17,916 --> 00:32:19,796 Speaker 1: I mean, I recognize that what you were doing is 566 00:32:19,836 --> 00:32:23,076 Speaker 1: distinct and particular, but it does seem like there is 567 00:32:23,116 --> 00:32:26,116 Speaker 1: this broader landscape that you were part of, where people 568 00:32:26,156 --> 00:32:31,596 Speaker 1: are using cells to treat disease, and people are thinking 569 00:32:31,676 --> 00:32:35,636 Speaker 1: about how to create new versions of skin and of 570 00:32:35,676 --> 00:32:38,916 Speaker 1: blood vessels, and are working on new ways of thinking 571 00:32:38,916 --> 00:32:42,476 Speaker 1: about organs and transplantation. I mean, what does the broader 572 00:32:42,556 --> 00:32:45,516 Speaker 1: landscape look like from your point of view and where 573 00:32:45,516 --> 00:32:46,916 Speaker 1: do you fit into it? And like what are the 574 00:32:46,956 --> 00:32:49,836 Speaker 1: big shifts, Like what do you expect to see in 575 00:32:49,876 --> 00:32:51,316 Speaker 1: the next five tenures? 576 00:32:52,076 --> 00:32:55,316 Speaker 2: Look, I think in ten years there is the realistic 577 00:32:55,396 --> 00:32:59,716 Speaker 2: possibility that at least in some cases like a liver transplant, 578 00:32:59,716 --> 00:33:04,196 Speaker 2: that those are relegated to medical history books, that the 579 00:33:04,236 --> 00:33:07,756 Speaker 2: notion of being on a wait list for an organ 580 00:33:08,436 --> 00:33:12,076 Speaker 2: will hopefully seem as foreign and strange to our children 581 00:33:12,076 --> 00:33:14,956 Speaker 2: and grandchildren. Like you talk to a grandparent, you're like, wait, 582 00:33:14,996 --> 00:33:19,116 Speaker 2: there were these sanatoriums with iron lungs everywhere. So I 583 00:33:19,156 --> 00:33:22,436 Speaker 2: think there's this opportunity that we really are going to 584 00:33:22,436 --> 00:33:26,156 Speaker 2: be turning the page from a medical history perspective, and 585 00:33:26,196 --> 00:33:30,076 Speaker 2: that there is the potential that in the really foreseeable future, 586 00:33:30,676 --> 00:33:33,396 Speaker 2: you're going to be the source of your own medicine. 587 00:33:33,876 --> 00:33:36,356 Speaker 2: You're going to be able to engineer your own cells 588 00:33:36,396 --> 00:33:39,596 Speaker 2: to avoid the problems of immune suppression and use them 589 00:33:39,716 --> 00:33:44,476 Speaker 2: in ways to induce remarkable regenerative outcomes, both in terms 590 00:33:44,556 --> 00:33:48,596 Speaker 2: of organ regeneration potentially in terms of lem regeneration, and 591 00:33:48,716 --> 00:33:52,996 Speaker 2: do things that again seem like science fiction today. Now 592 00:33:53,076 --> 00:33:55,436 Speaker 2: things always take longer and cost more than you hope. 593 00:33:55,436 --> 00:33:58,836 Speaker 2: But I do think when you look broad brushstrokes, we 594 00:33:58,956 --> 00:34:01,516 Speaker 2: really are on the cusp of a very exciting time. 595 00:34:01,556 --> 00:34:08,996 Speaker 1: That way, we'll be back in a minute with the 596 00:34:09,156 --> 00:34:20,756 Speaker 1: lighting round, and now we are going to finish with 597 00:34:20,796 --> 00:34:28,516 Speaker 1: the lightning round. You were a practicing clinical psychologist before 598 00:34:28,516 --> 00:34:32,116 Speaker 1: you got into the drug development business. Briefly, how did 599 00:34:32,156 --> 00:34:35,036 Speaker 1: that happen? Briefly? 600 00:34:35,156 --> 00:34:38,836 Speaker 2: I was very fortunate to work on some research methodologies 601 00:34:38,916 --> 00:34:41,236 Speaker 2: that were used widely in clinical psych but had a 602 00:34:41,276 --> 00:34:45,156 Speaker 2: lot of applicability and drug development, and so got involved 603 00:34:45,276 --> 00:34:49,596 Speaker 2: in consulting in that kind of niche area of research design, 604 00:34:50,436 --> 00:34:54,116 Speaker 2: and really just love the intersection of science and business 605 00:34:54,116 --> 00:34:57,476 Speaker 2: because you saw how much more rapidly you could you 606 00:34:57,516 --> 00:35:00,396 Speaker 2: could make progress, and how many more lives you could 607 00:35:00,396 --> 00:35:04,196 Speaker 2: affect than just writing publications. So and I'll also say 608 00:35:04,236 --> 00:35:06,676 Speaker 2: when you meet with the FDA, having those group psychotherapy 609 00:35:06,716 --> 00:35:08,396 Speaker 2: skills can come in remarkably helpful. 610 00:35:09,836 --> 00:35:11,916 Speaker 1: I feel like you're not joking when you say that. 611 00:35:11,996 --> 00:35:13,396 Speaker 1: It plays a joke, but. 612 00:35:15,236 --> 00:35:18,276 Speaker 2: You're you're right on that you kind of joke about 613 00:35:18,316 --> 00:35:21,236 Speaker 2: the skills of a clinical psychologist, but those key skills 614 00:35:21,276 --> 00:35:23,436 Speaker 2: in business settings being able to kind of take the 615 00:35:23,476 --> 00:35:26,316 Speaker 2: perspective of other people very rapidly and pick up on 616 00:35:26,756 --> 00:35:29,756 Speaker 2: concerns they may have that actually ends up being you know, 617 00:35:29,916 --> 00:35:32,676 Speaker 2: incredibly essential and regulatory interactions. 618 00:35:34,036 --> 00:35:38,316 Speaker 1: So you did research on smoking cessation in your previous 619 00:35:38,436 --> 00:35:42,196 Speaker 1: professional life. What's one thing that you learned about addiction 620 00:35:42,676 --> 00:35:43,436 Speaker 1: in your research. 621 00:35:44,516 --> 00:35:46,676 Speaker 2: You know that when you're trying to understand why some 622 00:35:46,716 --> 00:35:50,156 Speaker 2: people return to substance use, so much of it can 623 00:35:50,196 --> 00:35:55,356 Speaker 2: come down to momentary decisions and small slips and how 624 00:35:55,396 --> 00:35:57,956 Speaker 2: a single slip can lead to a full blown relapse, 625 00:35:57,996 --> 00:36:01,796 Speaker 2: but from that single slip people can recover and rebound, 626 00:36:02,596 --> 00:36:05,516 Speaker 2: and finding out how these fleeting life stressors can play 627 00:36:05,556 --> 00:36:09,556 Speaker 2: an incredibly large role in just kind of that chaos 628 00:36:09,596 --> 00:36:12,596 Speaker 2: of life that kind of pushes us on different trajectories 629 00:36:13,236 --> 00:36:16,876 Speaker 2: that ends up, you know, making you a smoker or 630 00:36:16,916 --> 00:36:19,396 Speaker 2: a non smoker or so is it just random? 631 00:36:20,036 --> 00:36:22,236 Speaker 1: I mean, what what do I what is the inference 632 00:36:22,236 --> 00:36:23,716 Speaker 1: from that? Like? What does that mean? 633 00:36:24,356 --> 00:36:26,316 Speaker 2: Yeah, well, you know, some of my work was actually 634 00:36:26,316 --> 00:36:30,156 Speaker 2: in something called catastrophe modeling, which was a subset of 635 00:36:30,196 --> 00:36:34,036 Speaker 2: chaos theory that kind of fundamental of the butterfly wings 636 00:36:34,036 --> 00:36:37,796 Speaker 2: causing the tornado, right, that these very small changes in 637 00:36:37,876 --> 00:36:41,836 Speaker 2: life can have this outsized impact, and it was it 638 00:36:41,876 --> 00:36:44,236 Speaker 2: was hard to avoid that conclusion when you look at 639 00:36:44,516 --> 00:36:46,756 Speaker 2: real time monitoring of folks trying to quit smoking. 640 00:36:48,076 --> 00:36:52,116 Speaker 1: So I understand you also run a nonprofit called Harm 641 00:36:52,156 --> 00:36:56,676 Speaker 1: Reduction Therapeutics that brought to market a generic over the 642 00:36:56,716 --> 00:36:58,636 Speaker 1: counter version of noloxone. 643 00:36:58,756 --> 00:36:59,436 Speaker 2: That's correct. 644 00:36:59,636 --> 00:37:04,396 Speaker 1: Briefly, how'd that happen? There was a huge. 645 00:37:04,196 --> 00:37:07,556 Speaker 2: Unmet need, as you know, as the opioid crisis unfolded. 646 00:37:07,956 --> 00:37:10,796 Speaker 2: Noloxone had been FDA proof since seventy one, it'd been 647 00:37:10,796 --> 00:37:14,116 Speaker 2: off patents since eighty five. It was an incredibly effective, 648 00:37:14,196 --> 00:37:19,516 Speaker 2: incredibly safe opioid overdose andidote, but for profit companies were 649 00:37:19,516 --> 00:37:23,076 Speaker 2: refusing to take their products over the counter because they 650 00:37:23,156 --> 00:37:26,156 Speaker 2: were making such high margins on them as prescription products. 651 00:37:27,076 --> 00:37:30,956 Speaker 2: Got extraordinarily frustrated with that set of circumstances when you 652 00:37:30,996 --> 00:37:34,196 Speaker 2: had over one hundred thousand Americans dying annually of opioid overdose. 653 00:37:34,876 --> 00:37:37,196 Speaker 2: So my colleague John pinion I formed a five oh 654 00:37:37,276 --> 00:37:41,516 Speaker 2: one C three nonprofit pharmaceutical company and ended up bringing 655 00:37:42,076 --> 00:37:45,916 Speaker 2: in over the counter three milligram Naloxo nasal spray and 656 00:37:46,076 --> 00:37:49,196 Speaker 2: doing it as a nonprofit. We entered the market at 657 00:37:49,236 --> 00:37:53,196 Speaker 2: about thirty six dollars worth thirty three dollars now at 658 00:37:53,236 --> 00:37:56,716 Speaker 2: the time Narcan was one hundred and forty dollars and 659 00:37:56,756 --> 00:37:58,996 Speaker 2: lo and behold, you can buy them now for about 660 00:37:59,076 --> 00:38:01,956 Speaker 2: mid thirty dollars per pack. So the hand of the 661 00:38:01,996 --> 00:38:04,996 Speaker 2: market did its job, you know, So we forced other 662 00:38:05,076 --> 00:38:07,356 Speaker 2: folks to go over the counter with their product, forced 663 00:38:07,436 --> 00:38:11,356 Speaker 2: them to lower their price. And yeah, that's something that 664 00:38:11,356 --> 00:38:14,956 Speaker 2: I was a very satisfying professional accomplishment to kind of 665 00:38:14,956 --> 00:38:18,396 Speaker 2: help the whole field move forward. So our product, Revive 666 00:38:18,556 --> 00:38:22,196 Speaker 2: is now this FDA approved over the counter three milligram 667 00:38:22,316 --> 00:38:26,676 Speaker 2: internasal noloxo nasal spray for emergency treatment of opioid overdose. 668 00:38:27,196 --> 00:38:31,156 Speaker 1: Last one, you've written that if you're running a startup, 669 00:38:31,196 --> 00:38:38,276 Speaker 1: you can only have three out of the following five things. Family, friends, sleep, exercise, 670 00:38:38,396 --> 00:38:42,156 Speaker 1: and hobbies. Which are your three? Oh? 671 00:38:42,316 --> 00:38:47,196 Speaker 2: Man, I'm very fortunate to have a family that I 672 00:38:47,236 --> 00:38:49,956 Speaker 2: adore and cannot spend enough time with, so I would 673 00:38:49,956 --> 00:38:55,796 Speaker 2: say family. I do exercise regularly. Oh I was so, 674 00:38:55,836 --> 00:38:56,636 Speaker 2: Hold on, what were. 675 00:38:56,556 --> 00:38:59,956 Speaker 1: The So you have to choose now one from the 676 00:38:59,996 --> 00:39:03,116 Speaker 1: following three? Friends, sleep, or hobbies. 677 00:39:04,836 --> 00:39:07,156 Speaker 2: I don't see near as much of my friends as 678 00:39:07,156 --> 00:39:10,996 Speaker 2: I would like, so I guess I would say hobbies 679 00:39:11,036 --> 00:39:13,636 Speaker 2: are the other thing that keep me grounded. 680 00:39:14,116 --> 00:39:18,756 Speaker 1: Also, you don't sleep. Unfashionable it's suddenly fashionable? 681 00:39:19,116 --> 00:39:21,476 Speaker 2: Yeah, exactly, exactly. 682 00:39:21,396 --> 00:39:23,556 Speaker 1: Not as much as i'd like. What's the hobby. 683 00:39:24,796 --> 00:39:29,236 Speaker 2: Amateur musician, so you know, kind of singer songwriter and yeah, 684 00:39:29,276 --> 00:39:32,876 Speaker 2: so amateur musician in my very spare time. 685 00:39:33,556 --> 00:39:35,676 Speaker 1: Is there a song of yours we should play under 686 00:39:35,716 --> 00:39:38,076 Speaker 1: the credits of today's show? Can you play us out? 687 00:39:40,036 --> 00:39:42,276 Speaker 2: I'll think about it. Sure, I'll send you something you 688 00:39:42,276 --> 00:39:42,796 Speaker 2: can play out. 689 00:39:42,916 --> 00:39:46,036 Speaker 1: Okay. It was delightful to talk with you. Thank you 690 00:39:46,076 --> 00:39:48,676 Speaker 1: for your time, Jacob. It was really, really nice. 691 00:39:49,476 --> 00:39:51,796 Speaker 2: These were wonderful questions. I actually really enjoyed the conversation. 692 00:39:56,076 --> 00:39:59,916 Speaker 1: Michael Hufford is the co founder and CEO of Like Genesis. 693 00:40:00,636 --> 00:40:03,956 Speaker 1: Today's show was produced by Gabriel Hunter Chang, edited by 694 00:40:03,996 --> 00:40:08,236 Speaker 1: Lydia Jean Kott, and engineered by Sarah Bruguer. I'm Jacob Goldstein. 695 00:40:08,476 --> 00:40:11,196 Speaker 1: Will be in the next couple of weeks off and 696 00:40:11,196 --> 00:40:14,236 Speaker 1: then we'll be back in the meantime. You can email 697 00:40:14,356 --> 00:40:17,156 Speaker 1: us at problem at pushkin dot fm, or you can 698 00:40:17,196 --> 00:40:20,916 Speaker 1: find me on LinkedIn or on x I'm at Jacob Goldstein. 699 00:40:21,316 --> 00:40:23,916 Speaker 1: Thanks for listening. We'll be back in a few weeks. 700 00:40:25,716 --> 00:40:39,756 Speaker 1: Oh sick, Oh sick.