Michael Hufford (3:50)

It is remarkable because it's the only organ in the human body that will naturally regenerate. So you can lose 70% of your liver, and over a course of just a few weeks, you will regenerate that liver entirely. And that's true only for the liver. And ironically, it's something We've known for 3,000 years. Right? The myth of Prometheus, if you might remember, the Titan that stole fire from Zeus and gave it to man was punished by being chained to a rock. And that eagle would come every day and eat his liver, and the punishment was eternal because his liver would regenerate and the eagle would have more liver to feast on the next day.

Jacob Goldstein (4:31)

I was vaguely familiar with the myth of Prometheus, but I was not familiar with the fact that the liver regenerates itself. I mean, do you infer that the Greeks knew that?

Michael Hufford (4:40)

Yeah, absolutely. I think they did know that. I think probably through the experiences and battle and what have you, you could, they could see that you could sustain a dramatic injury to the liver and that unlike any other organ, it would regenerate. But at the same time, it's taken us 3,000 years to get to the point that one, we can successfully transplant it. Right? That was the pioneering work of Dr. Tom Starzl. You know, he first attempted it in 1963, got it to work in 1967. It's saved tens of thousands of patients lives since then. And now ligenesis is really standing on the shoulders of folks like Dr. Starzl and now trying to regenerate the liver in other places in the body.

Jacob Goldstein (5:24)

Let me ask a nitpicky question before I ask a real question. Is the Skin, an organ. And does the skin regenerate itself?

Michael Hufford (5:33)

That's a good point. The skin has some ability to regenerate itself, for sure. And in fact, in children, if a small child loses the tip of a finger in an accident before the age of seven, you can actually regrow the tip of your finger. But we lose that remarkable ability to regenerate as we get older. And the only organ that retains that capability is the liver.

Jacob Goldstein (6:00)

So you mentioned liver transplants. Incredible life savings. Technology. Let's call it a technology. Why, why do we need lygenesis? Like what is the limit of liver transplants?

Michael Hufford (6:14)

Liver transplants. We have about 9,000 patients on the US currently for a liver transplant. 15 to 20% of those patients will die each year awaiting a liver transplant to become available. So I would say it's. There's really a fundamentally a twofold problem. One is supply and demand. Today we, one donated organ treats one patient using our technology, a single donated organ, because we're isolating the individual liver cells or hepatocytes from that liver. A single donated organ could treat 50 patients. So one, we're kind of fixing and really upending the supply, demand calculus when it comes to, you know, instead of one donated organ treating one patient, with our approach, one donated organ can treat up to 50 patients. But the other problem is what oftentimes people aren't aware of, which is for all the understandable human drama of a liver transplant wait list of all the organ transplant wait lists where people are waiting for this life saving gift of organ donation, many patients are too ill to even make the list. So in the US you have about 5 million cases of end stage liver disease in one form or another. You have 85,000 deaths. At least 50% of the patients that could benefit from an organ transplant don't qualify because we know that they simply won't survive the procedure because it's a

Jacob Goldstein (7:41)

big open surgery that involves a lot of trauma and if you're very sick already, you'll probably die from the surgery.

Michael Hufford (7:47)

Yes, correct.

Jacob Goldstein (7:48)

So you co founded the company with scientists, with a researcher named Eric Lagasse. Right. And it was based on research that he had done. So tell me about meeting him, where you were and what was the work he had done that you found so compelling that you had to go start a company with him?

Michael Hufford (8:06)

Yeah, absolutely. So Eric Legasse is a Professor at the McGowan Institute for Regenerative Medicine and Pathology at the University of Pittsburgh. At the time, I was an entrepreneur in residence at the University of Pittsburgh and I had spent 25 years doing drug development and had been fortunate to work on a number of very innovative programs and had started and sold a number of companies. And so was working with the University of Pittsburgh because they get almost billion dollars of NIH funding annually. It's a remarkable research enterprise, both at the University of Pittsburgh and the University of Pittsburgh Medical center, or upmc. And so they wanted to get more companies spun out as a function of that funding. And so one day, a colleague of mine took me to meet Eric Legasse. And what Eric told me was a remarkable story in two ways. One, he showed me these remarkable pictures from his publication in Nature Biotechnology, showing that he could regrow organs in the lymph nodes of mice, that he could take liver cells from a mouse, engraft them into the lymph node of another mouse. These animals had a genetic liver disease as a function of that liver disease, they would otherwise die from that liver disease. But when he engrafted these hepatocytes into their lymph nodes, those lymph nodes acted as living bioreactors. And they literally grew those animals, miniature livers, so that instead of dying from their liver disease, 100% of them were rescued from that otherwise fatal liver disease. So he had these pictures that were truly jaw dropping, you know, of these ectopic organs in places in the body that they should not otherwise be.

Jacob Goldstein (9:47)

So I just want to repeat what you just said, because it is the central extraordinary fact of the thing that you are doing. Right. What Legaste did was he had put liver cells, just cells into the lymph nodes of these mice that had liver disease. And within the lymph node, there grew a teeny liver that worked, that did what the big liver needed to do, and the mice didn't die. Like, why should that even be true?

Michael Hufford (10:19)

Yeah. So two things. One, um, over time, the lymph node disappears. The lymph node acts as a temporary bioreactor to get that ectopic organ. And by ectopic, we just mean in a different place in the body, that ectopic liver to grow. And in fact, those ectopic livers in mice could grow to 70% the size of a normal liver. So he could grow really quite large ectopic livers using these lymph nodes.

Jacob Goldstein (10:44)

And that doesn't mess the mice up? It doesn't, like, mess up their lymphatic system or something like that?

Michael Hufford (10:49)

Yeah, yeah. So remarkably, we've seen no untoward effects on the immune system. Now, partly because. Let's stop and Talk about lymph nodes for a second. Right. So lymph nodes in the human body, we have 450 to 700 lymph nodes spread throughout our body, a majority in our gut area. Right. And they've helped us as a species survive infection. Right. Because what a. What a lymph node does as its primary evolutionary function is help bioreact T cells. So when you develop a cold, you have a sore throat, and you feel that nodule, that kind of, you know, marble, or maybe even, you know, large marble underneath your jaw, that's a lymph node that's bioreacted billions of T cells to help you fight that infection.

Jacob Goldstein (11:35)

When you say bioreact, you basically mean grow, right? It is. Or create.

Michael Hufford (11:40)

Yes, it is, admittedly biotech jargon term for grow. That's exactly right.

Jacob Goldstein (11:45)

Okay, so the lymph node is a really good place for cells to grow. That's one reason it works, or it works in animals. You said there were two reasons. What's the other reason?

Michael Hufford (11:55)

The other is what's special about the liver and why even the Greeks knew that it would regenerate under the right circumstances. Is the fundamental cell of the liver is the hepatocyte. Hepatocytes are naturally regenerative. And so Eric's fundamental scientific discovery was that if you combine that natural regenerative potential of the hepatocyte with the natural ability of the lymph node to bioreact cells, you get this remarkable effect. And you could think of it as the flip side of the cancer coin. You know, many people are aware that cancer probes the environment to form tumors. And very often cancer will grow tumors in someone's lymph nodes.

Jacob Goldstein (12:43)

Right. And in fact, the classic sort of staging question in cancer is, has it spread to the lymph nodes? And if it has, in the case of cancer, that is bad.

Michael Hufford (12:53)

That is bad. Exactly right. Precisely because lymph nodes are such effective bioreactors and they are agnostic as to what they bioreact.

Jacob Goldstein (13:01)

You know, they're so good at growing cells.

Michael Hufford (13:03)

Yeah, exactly right. So if a cancer cell gets in there, the cancer cell thinks, man, this is a fantastic place. I have access to nutrients, and I have a confined space that I can focus on growth. And what you end up are these. Is the spread of these tumors.

Jacob Goldstein (13:19)

Right.

Michael Hufford (13:19)

Well, what Eric realized is that you could turn that biology to it, to a therapeutic instead of a malignant potential. So by putting a cell therapy like a hepatocyte into a lymph node you could generate functional tissues that exerted life saving effects. And so he showed me those first pictures from his study and it really was jaw dropping. And I asked him that afternoon what I thought was the gotcha question because it so often is with academic minded professors. I said, well, you know, that's great, Eric. It's incredibly impressive. What about large animals?

Jacob Goldstein (13:55)

Right? It's good news for mice, right?

Michael Hufford (13:58)

Exactly.

Jacob Goldstein (13:59)

The phrase mice lie and primates exaggerate drug development.

Michael Hufford (14:03)

I love that. I had not heard that before.

Jacob Goldstein (14:05)

No, somebody told me that 25 years.

Michael Hufford (14:08)

That's fantastic. I'm going to steal it, actually. That's wonderful. So. And he said, oh yeah, Michael. And in fact, his, his, his colleague, Dr. Paolo Fontes, who was our co founder and chief medical officer, showed that the exact same principle applied in pigs. So they showed that you could take a pig that would otherwise die from a fatal liver disease and you could rescue that pig using the exact same procedure. And they even tried a different model where they surgically injure the liver. So there's something called a portacaval shunt where you can go in and kind of rearrange the plumbing of the liver, so to speak, to deprive it of blood flow, which was a procedure that Dr. Starzl had pioneered as a way to test and develop the procedure that would eventually become liver transplantation, and again rescued those animals. And he told me something that as a drug developer, you, you virtually never hear. He said, michael, I can't get this not to work. And as a drug developer, right. I'd spent my entire career and the entire industry really is focused on getting the exact right drug delivered in the exact right way to the exact right patient at the exact right dose, oftentimes at the exact right time of day, and you hope for an effect. And what Eric was telling me was that nature had kind of primed this approach between the natural regenerative capacity of the liver and the natural bioreactor capabilities of the lymph node. And that when he said he couldn't get it not to work, quite literally, the hairs on the back of my neck stood up. And I said, okay, let's back up and go over this whole story again. You know, and, and, and really that, that day was the genesis of, of the company.

Jacob Goldstein (15:48)

So you start the company nine years ago, is that right? 2017.

Michael Hufford (15:54)

Yeah, yeah. Time has flown.

Jacob Goldstein (15:56)

Yeah, yeah. I mean, it takes a long time to develop new therapies, Right. This is regenerative medicine, cell therapy, a hard new thing to do. So where are you now, nine years later.

Michael Hufford (16:09)

Yeah. So we are now running a first in human phase 2, a clinical trial. So this is a clinical trial in patients with end stage liver disease. These are patients, most of them, not all. Most are on the liver transplant wait list. And they can come into the trial. They may have any number of different types of liver disease, but we're going for patients who have end stage liver disease that typically have a life expectancy of many months or a few years.

Jacob Goldstein (16:40)

Okay.

Michael Hufford (16:41)

Because we know that one limitation of our approach is that when you engraft these cells, they do take time to organize themselves. It's not like the next day you have a fully functioning ectopic liver. We know that it takes probably two to three months is our best gu. And so we want to make sure that these patients have the time to have the potential beneficial effects of the therapy. So we've now transplanted our first cohort of patients. There were four patients, all done at the Houston Methodist Hospital. Like you, typically, the phrases, you start low and go slow, you start low in dose and go slow because you're not sure what the effect will be. And so the FDA had counseled us. This first trial is just going to be 12 patients. Okay. So we have three different dose groups. We've completed that first dose cohort and we had a data safety monitoring board meeting where they look at all the safety data and the efficacy data to date. And they said, okay, you know, it's looking good. Let's. Let's go on and dose escalate as per the protocol. And so that's, that's what we are in the midst of right now.

Jacob Goldstein (17:47)

When are you gonna know if it worked? If this trial, you know, had a positive result that'll allow you to move to, presumably the next bigger trial?

Michael Hufford (17:58)

Yeah, we should have a very good sense of that in the middle part of next year. Okay. So the middle part of 20, 27, and then, yeah, move on from there.

Jacob Goldstein (18:06)

So let's talk about how it works. So there's a patient, as you've said, who is, you know, has liver disease, has some liver function left, but it's not looking good for them. And then there is, what, a donated liver. Like what, what actually happens?

Michael Hufford (18:23)

That's exactly right. When the organ becomes available. If, if the organ is eligible for transplant, then it's transplanted into a patient that needs it. Some organs, though, are not eligible for transplant. And that can be for any number of reasons. They may have been injured because of the cause of death. They might be a little fatty where when the transplant surgeon looks at the organ, they think, ah, you know, that's, that's not going to be a great fit for this particular patient. And so that they pass on it when they come to us. We then have a facility at Houston Methodist currently where we can take that organ. And it takes us just about four or five hours. It's a 70 plus step process, but we start with the full organ and after 70 steps and about, you know, four to five hours, we've isolated and suspended those hepatocytes into a solution that we then courier over to the endoscopic ultrasound suite.

Jacob Goldstein (19:24)

And so just to be clear, when you say the hepatocytes are in a solution, it's like a bottle full of liver cells in liquid.

Michael Hufford (19:33)

Yeah, that's exactly what it is. It's a small syringe, really, because we're only injecting about. Yeah, about 1 milliliter of the cell suspension, but it's literally like a browned, thick liquid.

Jacob Goldstein (19:48)

That's exactly, yeah. So a syringe like what? Like you'd get in a shot, but instead of a vaccine, it's liver cells from a donated liver. Okay, so then you courier that over to go. Go on. Yeah, yeah.

Michael Hufford (19:58)

And so the patient is put under light sedation. And just the way you might have an endoscope, you know, to look to see if you have an ulcer or to, you know, have any number of diagnostic procedures.

Jacob Goldstein (20:09)

Yes.

Michael Hufford (20:09)

Basically an endoscopist takes that endoscope under sedation down through the mouth of the patient. Okay. And then threads it down their GI tract, kind of into their gut area. And at the end of that endoscope is an ultrasound.

Jacob Goldstein (20:25)

Okay.

Michael Hufford (20:26)

And so the ultrasound, you can basically look adjacent to the gut wall and lymph nodes there show up as they almost look like bubbles to the untrained eye. Right. So they kind of look like these bubbles that come into view via the ultrasound.

Jacob Goldstein (20:42)

Okay.

Michael Hufford (20:43)

And. And the endoscopist takes a five foot needle that threads down through the endosing. Yeah, yeah. It then goes through the gut wall and punctures into the lymph node.

Jacob Goldstein (20:55)

Uhhuh. So it's like a shot. It's like a shot, but it's going into your stomach, across the wall of your stomach and into the lymph node.

Michael Hufford (21:04)

That's exactly right. That's exactly right. And so this takes about 10 minutes to find the lymph node and inject the CEL. So we inject 1 milliliter into that lymph node. They Withdraw the needle and pull the scope out. And the procedure itself at that point is done. The cells are in the lymph node. The patient's put on immune suppression.

Jacob Goldstein (21:27)

Right? The patient's put on immune suppression because these are cells from somebody else. So it's just like if you get a transplant, your body's cells will be like, oh, that's foreign. I'm gonna get rid of it.

Michael Hufford (21:37)

That's exactly right, yeah.

Jacob Goldstein (21:38)

Okay, so the patient's put on immune suppression, and then if it works, what happens?

Michael Hufford (21:45)

If it works, what happens is those cells find themselves in an environment that they find very comforting and very nourishing. And so they use those bioreactor aspects of the lymph node, begin dividing, because they're natural stem cells, and they begin organizing themselves into liver lobules, which are these little hexagonal collections of cells that are kind of the functioning filtering unit of the liver. And from all of our preclinical data, in both small and large animals, that division will continue to go on, and the vascularization will then occur. So the lymph nodes are, well, vascularized anyway. But what you find is that these ectopic organs recruit cells from the patient's body to form additional vasculature. So additional blood flow to that ectopic organ. So that over time and again, our best guess is it's over a few months of time. What you'll be left with is this functioning ectopic organ.

Jacob Goldstein (22:52)

So I'm picturing one, like, tiny little mini liver, like, I don't know, how big is it? Is there only one? How big does it have to be, or how many do there have to be for it to be clinically useful?

Michael Hufford (23:06)

They can get quite large. In small animals, you can get up to 70% of the native liver grown in a lymph node. In the larger animals, it was a smaller percentage. And your question about clinically meaningful, when you talk to hepatologists or folks like our Chief Medical Officer, Dr. Fontes, who's treated these patients across his entire life, if you can bump the functional amount of liver for one of these patients by 10 to 20%, you will alleviate a lot of the signs and symptoms of their end stage liver disease. And in fact, end stage liver disease is a problem because very often patients don't know that they have advanced liver disease until pretty far along, because it is a redundant system. As a species, we have very large livers to help us with the various things that we might eat and get exposed to. So it's a redundant system. And by the time you know you have a problem, you know you really have a problem. And so that's why we think if we can even bump it up by 10 to 20%, I think this will be a transformative therapy. So, you know, we envision clinically the potential both to treat patients that are never going to get an organ because they simply don't qualify for the list. But for others, it may be more clinically. What you're doing is just buying them time so that an organ can become available for them.

Jacob Goldstein (24:30)

We're gonna take an ad break right now, and then we're gonna come back and talk about a bunch more things, including why what Michael and Light Genesis are working on might not work. I'm not like a coffee connoisseur, but recently I tried coffee from a company called Perc and I loved it. And I'm not just saying that because this is an ad for Perc, though. This is an ad for Perc. I really did think the coffee was delicious. The bag I'm drinking at the moment was grown in Peru. Perc sources coffee from all over the world. They have lots of different kinds of coffee to choose from, and they color code their bags. Blue bags are more mild coffee and pink bags are more wild coffee. That Peruvian coffee I'm drinking now is wild, and if you're on the fence, I recommend trying wild. The other morning I had my first sip and I thought of that Will Ferrell line in old school where he hits the beer bong and then he says once it hits your lips, it's so good. Find the coffee that matches your vibe and get 15% off your next order with promo code problem@percccoffee.com that's P E R C coffee.com promo code problem small businesses are the pulse of every community. They bring people together, create opportunities, and drive growth. With a widespread presence in communities across the country, Chase for Business supports small business owners at a local level that makes it possible for you to connect, learn from each other, and grow together. There's a real commitment to seeing small businesses succeed. The Chase for Business team has knowledge and expertise that span a wide range of financial areas. They can help you make more informed choices as you navigate the complexities of running your business. They'll help your business grow with individual guidance and convenient digital tools all in one place. With that guidance and your determination, you can take your business farther and help build a brighter future for your community. Learn more@chase.com business chase for business make more of what's yours. The Chase Mobile app is available for select mobile devices. Message and data rates may apply. JP Morgan Chase Bank Naomi Member FDIC Copyright 2026 JPMorgan Chase Co. Run a

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Jacob Goldstein (27:50)

I wanna go back to one detail or one step. You mentioned of what happens inside the body in this process, and that is after the cells have been injected. They're just cells. They're just random liver cells floating around. And you said they organize themselves essentially into a liver. Into a little liver. You didn't say into a little liver. But that is essentially what's happening. Yeah, that part that seems like the central shocking thing that is going on here. Right. And I've talked to a couple of other people doing regenerative medicine and other way, somebody doing bones, somebody doing blood vessels, and they both use this term that I think I've seen you use elsewhere and that I'm reminded of here. And that is. It's more of a phrase that is that cells are intelligent cells have some intelligence which is not intuitive, but. But I'm reminded of it here, like, what's going on? How does that work?

Michael Hufford (28:53)

It's a great question and in fact, it's almost a testimony to why lygenesis exists that many academic researchers that never found companies can get not distracted because it's really the fundamental scientific pursuit of why and how. But to Eric's credit, when he. This is a long.

Jacob Goldstein (29:10)

You don't know is the answer. You don't know.

Michael Hufford (29:15)

You're absolutely right. The short answer is we don't know. The longer answer is, yeah, that. Well, short answer is we don't know. 2. I think you're right. The cells are Remarkably intelligent. And we know there's those dozens of pro growth sign from the diseased liver. We know they play a role, but exactly how it works, I'm thankful, let's put it this way, that Eric focused on trying to get it not to work because he ended up finding that it was so robust where, you know, a lot of researchers would spend their whole life trying to understand the why

Jacob Goldstein (29:47)

and how well and clearly in other organs or body parts. Like I remember in the case of blood vessels. And this is a classic challenge when people are trying to grow organs or mini organs is they do a lot of work to create the scaffolding, to create the structure. Right. And so the fact that in this instance it is naturally self organizing solves what seems to be the largest problem, or at least a key problem for many other organs.

Michael Hufford (30:20)

I would just say, yeah, it is better to be lucky than good. And that really is a case where

Jacob Goldstein (30:24)

pick the right organ. Yeah.

Michael Hufford (30:26)

Nature has really engineered this in a lot of respects. Right. Like as, as a drug developer. So often you're trying to trick the body. Right. Like, like you're trying to trick it to do something that's unnatural and, and, and have to fight against it all along the way. I think what excites me about regenerative medicine, but l genesis in particular, is that we just have a lot of headwinds because of evolution and biology. Then the naturally regenerative capability of the liver, the natural ability of the lymph node to bioreact a variety of tissues because Eric's shown that it's not just hepatocytes and ectop livers he can grow. He can put pancreatic islets and rescue animals that have diabetes by putting those islets into lymph nodes. He can put the thymus from a young animal into the lymph node of an old animal and help reboot that old animal's immune system. And in fact, the whole animal starts to look more youthful physiologically as a function of that. So I think the lymph node is going to act as a platform for a variety of different tissues. And so at ligenesis, the liver is certainly the most far along of the assets we have. But we also have this work on the thymus and the kidney and the pancreas because as I said, the lymph node, it's just remarkably agnostic about the type of tissue that it bioreacts.

Jacob Goldstein (31:51)

And just to be clear, that other work that is not yet in humans, right. That is earlier you're in clinical. Correct. That's exactly right. Yeah.

Michael Hufford (31:58)

Correct.

Jacob Goldstein (31:59)

In the liver trial, which is the one that's the farthest along. So let's talk about that. What might go wrong?

Michael Hufford (32:05)

Why might it not work in terms of. Of. Of what might go wrong? Our body's ability to reject what's called allogeneic, which is just the medical term. Right. For. From another. From another person, say, from another animal. Our body's ability to do that has been central to our success as a species. And as a result, when you try to get around it, you have to use very powerful drugs to try to convince it not to reject those cells. And so I think acute rejection, especially when you're injecting a relatively small number of cells as compared to a very large organ, I think that's one thing that you worry about.

Jacob Goldstein (32:46)

Oh, the small number of cells. Because it's, like, easier for the body with its immune response to wipe out a small number of cells.

Michael Hufford (32:53)

Exactly right. Yeah.

Jacob Goldstein (32:54)

Dumb question. I mean, I sort of know the answer, but presumably the patients with liver disease have some of their own liver cells left.

Michael Hufford (33:03)

Yes.

Jacob Goldstein (33:04)

What if you took some of their own liver cells and put them in the lymph node? You wouldn't have the rejection problem.

Michael Hufford (33:10)

That's a great question, and we get that a lot. For the patients that we're targeting with end stage liver disease, the liver is also prone to potentially catastrophic bleeding risk. And so the notion of biopsying a fibrotic liver is one that has, you know, very significant medical risks associated with it.

Jacob Goldstein (33:30)

Okay, another one, I'm just gonna. This one I'm just making up. Can you do, like, induced pluripotent stem cells from the patient and turn them into liver cells?

Michael Hufford (33:42)

That's. That is exactly our vision, actually, for our. For our second generation therapy. So our first generation therapy is going to be these allogeneic cells. The second generation will be exactly that. The hope. And there are labs around the world working on this. No one's solved it yet. But induced pluripotent stem cells, where you take a skin cell and you push it back to a more embryonic, like, state and then bring it forward as a different cell type. You know, we've had tremendous success in a variety of cell types. To have a fully mature human hepatocyte is something that no one's been able to do yet.

Jacob Goldstein (34:15)

Nobody's been able to get a stem cell to turn into a mature human liver cell.

Michael Hufford (34:20)

Exactly.

Jacob Goldstein (34:21)

So, okay, so immune rejection, that's one problem. What else?

Michael Hufford (34:25)

You know, one thing that we didn't worry a lot about, but just because we had endoscopic colleagues that assured us this was a very safe procedure. But, you know, I've taken several drugs first into human. You always worry. And so with patients with bleeding risk, you know, the endoscopic ultrasound is something that you want to make sure goes well. But again, we're using incredibly talented endoscopists. They do the same procedure to look for patients who've been newly diagnosed with pancreatic cancer. The good news is we're asking endoscopists to do something they're very familiar with, using equipment they're very familiar with. But still, you always worry about, you know, you're going through the gut wall with a needle and into a lymph node. And, you know, you always want that to go well. And at this point, we've had no serious adverse events from. From the administration itself. But that's something, you know, that's why you start low and go slow, as they say. Right. In these. First in human trials and then.

Jacob Goldstein (35:19)

So these are the sort of technical risks or medical risks. Is there like running out of money? I mean, a biotech company with no product, like, how's. How's that part of it?

Michael Hufford (35:32)

Sure, yeah. There's always business risk. You know, I was told a long time ago that the. The definition of a biotech is a company unencumbered with revenues and you don't

Jacob Goldstein (35:43)

have to worry about the profit and loss statement because.

Michael Hufford (35:45)

Exactly. P L is very. Yeah, we only have half of it. So I will say that, yeah, you always worry about running out of money. Drug development always takes longer and costs more than you hope it will. Even when you've done it a long time, there's always surprising challenges. I will say, you know, we're fortunate to have wonderful investors that are patient with us despite the inevitable setbacks as we push forward. As a drug developer, you're. You're always taught that great drugs are killed at least three times right before they actually make it over the finish line. So we have, we have folks that are with us and supporting us and, and we've tried to be very capitally efficient. Like Genesis is just half a dozen people. We've raised under $40 million to date where when you look at the typical cost to get an investigational new drug clearance by the FDA or an IEP that usually costs hundreds of millions of dollars. And just, you know, we've been fortunate to not need a staggering amount of capital to get to where we are, which is in the clinic, in Part because of the NIH funding that Eric Legasse had at the University of Pittsburgh. And it really is why the NIH cuts that we've seen happen really are undermining the kind of future potential of so many new therapies and technologies that you're simply not going to hear about, because the funding wasn't available for them to move forward. But thankfully, Eric's work was very well funded by the nih, and so we've been able to take it forward.

Jacob Goldstein (37:11)

So I just want to talk for a minute more broadly about. I was trying to decide, should we talk about cellular therapy or regenerative medicine? Right. You're kind of both, if I'm sort of reading the world. Right. But I'm not sure. I mean, I recognize that what you were doing is distinct in particular, but it does seem like there is this broader landscape that you are part of where people are using cells to treat disease and people are thinking about how to create new versions of skin and of blood vessels and are working on new ways of thinking about organs and transplantation. I mean, what does the broader landscape look like from your point of view? And where do you fit into it? And, like, what are the big shifts? Like, what do you expect to see in the next five, 10 years?

Michael Hufford (38:00)

Look, I think in 10 years there is the realistic possibility that at least in some cases, like a liver transplant, that those are relegated to medical history books, that the notion of being on a wait list for an organization will hopefully seem as foreign and strange to our children and grandchildren. Like, you talk to a grandparent, you're like, wait, there were these sanatoriums with ironed lungs everywhere. Like, so I think there's this opportunity that we really are going to be turning the page from a medical history perspective and that there is the potential that in the really foreseeable future, you're going to be the source of your own medicine. You're going to be able to engineer your own cells to avoid the problems of immune suppression and. And use them in ways to induce remarkable regenerative outcomes, both in terms of organ regeneration, potentially in terms of limb regeneration, and do things that, again, seem like science fiction today. Now, things always take longer and cost more than you hope, but I do think when you look broad, brushstrokes. We really are on the cusp of a very exciting time now.

Jacob Goldstein (39:16)

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Jacob Goldstein (42:27)

Now we are gonna finish with the lightning round. You were a practicing clinical psychologist before you got into the drug development business? Briefly. How did that happen?

Michael Hufford (42:42)

Briefly? I was very fortunate to work on some research methodologies that were used widely in clinical psych, but had a lot of applicability in drug development and so got involved in consulting in that kind of niche area of research design and really just loved the intersection of science and business because you saw how much more rapidly you could, you could make progress and how many more lives you could affect than just writing publications. So. And I'll also say when you meet with the fda, having those group psychotherapy skills can come in remarkably helpful.

Jacob Goldstein (43:16)

So I feel like you're not joking when you say that. It plays as a joke, but you're,

Michael Hufford (43:24)

you're right on that. You kind of joke about the skills of a clinical psychologist, but those key skills in business settings, being able to kind of take the perspective of other people very rapidly and pick up on concerns they may have, that actually ends up being, you know, incredibly essential in regulatory interactions.

Jacob Goldstein (43:42)

So you did research on smoking cessation in your previous professional life. What's one thing that you learned about addiction in your research?

Michael Hufford (43:52)

You know that when you're trying to understand why some people return to substance use, so much of it can come down to momentary decisions and small slips and how a single slip can lead to a full blown relapse. But from that single slip, people can recover and rebound. And finding out how these fleeting life stressors can play an incredibly large role in just kind of that chaos of life that kind of pushes us on different trajectories that ends up, you know, making you a smoker or a non smoker.

Jacob Goldstein (44:26)

So is it just random? I mean, what, what do I, what, what is the inference from that? Like, what does that mean?

Michael Hufford (44:32)

Yeah, well, you know, some of my work was actually in something called catastrophe modeling, which was a subset of chaos theory, that kind of fundamental of, of the butterfly wings causing the tornado. Right. That these very small changes in life can have this outsized impact. And it was, it was hard to avoid that conclusion when you look at real time monitoring of folks trying to quit smoking.

Jacob Goldstein (44:56)

So I understand you also run a nonprofit called Harm Reduction Therapeutics that brought to market a generic over the counter Version of naloxone.

Michael Hufford (45:06)

That's correct.

Jacob Goldstein (45:07)

Briefly, how'd that happen?

Michael Hufford (45:11)

There was a huge unmet need, as you know, as the opioid crisis unfolded. Naloxone had been FDA approved since 71, had been off patents since 85. It was an incredibly effective, incredibly safe opioid overdose antidote. But for profit companies were refusing to take their products over the counter because they were making such high margins on them as prescription products. They got extraordinarily frustrated with that set of circumstances when you had over 100,000Americans dying annually of opioid overdose. So my colleague John Pinion and I formed a 501c3 nonprofit pharmaceutical company and ended up bringing an over the counter 3 milligram naloxone nasal spray and doing it as a nonprofit. We entered the market at about $36. We're at $33 now. At the time, Narcan was $140.

Jacob Goldstein (46:04)

Wow.

Michael Hufford (46:04)

And lo and behold, you can buy them now for about mid $30 per pack. So the hand of the market did its job, you know, so we forced other folks to go over the counter with their product, forced them to lower their prices. And yeah, that's something that was a very satisfying professional accomplishment to kind of help the whole field move forward. So our product revive is now this FDA approved over the counter 3 milligram intranasal naloxone nasal spray for emergency treatment of opioid overdose.

Jacob Goldstein (46:35)

Last one. You've written that if you're running a startup, you can only have three out of the following five things. Family, friends, sleep, exercise, and hobbies. Which are your three?

Michael Hufford (46:50)

Oh, man. I'm very fortunate to have a family that I adore and cannot spend enough time with. So I would say family. I do exercise regularly. Oh. So hold on. What were the.

Jacob Goldstein (47:06)

So the. You have to choose now one from the following three. Friends, sleep or hobbies.

Michael Hufford (47:13)

I don't see near as much of my friends as I would like, so I guess I would say hobbies are the other thing that keep. Keep me grounded.

Jacob Goldstein (47:22)

Ah. Also, you don't sleep unfashionable. It's suddenly fashionable to sleep?

Michael Hufford (47:27)

Yeah, exactly, exactly. Not as much as I'd like.

Jacob Goldstein (47:30)

What's the hobby?

Michael Hufford (47:33)

Amateur musician. So, you know, kind of singer, songwriter and. Yeah. So amateur musician in my very spare time.

Jacob Goldstein (47:41)

Is there a song of yours we should play under the credits of today's show? Can you play us out?

Michael Hufford (47:48)

I'll think about it. Sure. I'll send you something you can play out.

Jacob Goldstein (47:51)

Okay. It was delightful to talk with you. Thank you for your time, Jacob.

Michael Hufford (47:55)

It was really, really nice. These were wonderful questions. I actually really enjoyed the conversation.

Jacob Goldstein (48:04)

Michael Hufford is the co founder and CEO of Light Genesis. Today's show was produced by Gabriel Hunter Chang, edited by Lydia Jean Cott, and engineered by Sarah Bruguerre. I'm Jacob Goldstein. We'll be taking the next couple of weeks off and then we'll be back. In the meantime, you can email us at Problemushkin FM or you can find me on LinkedIn or on X. I'm at Jacob Goldstein. Thanks for listening. We'll be back in a few weeks. I'm not like a coffee connoisseur, but recently I tried coffee from a company called Perk and I loved it. And I'm not just saying that because this is an ad for Perc, though. This is an ad for Perk. I really did think the coffee was delicious. Perk has lots of different coffees to choose from and they color code their bags. The blue bags are mild coffee, the pink bags are wild coffee. You can find the coffee that matches your vibe and get 15% off your next order with promo code problem@percccoffee.com that's P E R C coffee.com promo code

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