Jan. 19, 2023

#102: Jan Jensen (Trailhead Biosystems)

Jan Jenson — Ph.D., CEO/CSO/Founder of Trailhead Biosystems — on the basics of cell differentiation and development biology, and the vast implications that unlocking industrialized manufacturing of specialized human cells can have for regenerative medicine

Lay of The Land's conversation today is with Jan Jenson — PhD, CEO/CSO/Founder of Trailhead Biosystems, based here in Cleveland.

Jan is the Lead Inventor of Trailhead Technology and has 20 years as a molecular developmental biologist. He is the Eddie J. Brandon Endowed chair of Diabetes Research at the Cleveland Clinic and obtained his Ph.D. from U. Copenhagen in 1998 and has been faculty at US institutions since 2001 where he has published more than 50 peer-reviewed papers and is now engaged with multiple research projects and consortia covering neural, renal, pancreatic areas, as well as cancer and immunotherapy.

The technology of Trailhead Biosystems — which exists around the high-dimensional design of experiments dependent on computerized designs and robotic executions — allows for the production of cellular ink as the biological building blocks to address a myriad of issues across cell-based therapeutics, drug discovery, organ printing, and disease modeling — ultimately aiming to arrive at the cures for diseases we’ve only historically been able to treat like Diabetes, which is one of Jan’s original motivations.

Trailhead Biosystems is one of the most fascinating companies I’ve come across so far and I learned so much from this conversation with Jan — everything from the basics of cell differentiation and development biology, to the vast implications that unlocking industrialized manufacturing of specialized human cells can have for regenerative medicine! Please enjoy my conversation with Jan Jensen

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Learn more about Trailhead Biosystems
Connect with Jan Jensen on LinkedIn


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Transcript

Jan Jensen (Trailhead Biosystems) [00:00:00]:
This is what brought me into this space initially is the hope that, you know, we can we we can get beyond insulin treatment but move into curing people instead. Why do we have to inject every single day? Why do we have to be worried? Why do we have to have these complications? All the problems associated, say, living with diabetes for a lifetime when the cure is so obvious, just put new cells in. It has been the thing that has always driven me, the simplicity of addressing that is there, but the complexity of making the cell has always been the thing that has followed.

 

Jeffrey Stern [00:00:42]:
Let's discover the Cleveland entrepreneurial ecosystem. We are telling the stories of its entrepreneurs and those supporting them. Welcome to the Lay of the Land podcast, where we are exploring what people are building in Cleveland. I am your host, Jeffrey Stern, and today, I had the real pleasure of speaking with Jan Jensen, PhD, CEO, and founder of Trailhead Biosystems based here in Cleveland. Jan is the lead inventor of Trailhead Technology and has 20 years as a molecular developmental biologist. He is the Eddie j Brandon endowed chair of diabetes research at the Cleveland Clinic and obtained his PhD from the University of Copenhagen in 1998 and has been a faculty at US Institutions since 2001, where he has published more than 50 peer reviewed papers and is now engaged with multiple research projects and consortia covering neural, renal, pancreatic areas, as well as cancer and immunotherapy. The technology of Trailhead Biosystems, which exists surrounds the high dimensional design of experiments dependent on computerized designs and robotic executions, allows for the production of cellular ink as the biological building blocks to address a myriad of issues across cell based therapeutics, drug discovery, organ printing, and disease modeling, ultimately aiming to arrive at the cures for diseases we've historically only been able to treat, like diabetes, which is one of Jan's original motivations. Trailhead Biosystems is one of the most fascinating companies I've come across so far, and I have learned so much from this conversation with Jan.

 

Jeffrey Stern [00:02:23]:
Everything from the basics of cell differentiation and developmental biology to the vast implications that unlocking industrialized manufacturing of specialized human cells can have for regenerative medicine. So please enjoy my conversation with Jan Jenssen. So more and more these days, I feel like I am hearing about biology, developmental biology, synthetic biology, as kind of the next great frontier and and where we can realize, you know, some of the the greatest gains for human development going forward. And and with that, I am excited to hear about all the work you're doing in the space. And I wanna start maybe with just how you found yourself in the space. You know, where where did you come to develop your your passion for for biology?

 

Jan Jensen (Trailhead Biosystems) [00:03:18]:
Oh, thank you, Jeffrey. I mean, it wasn't planned at all. It was a my my career has more or less been If if if the group went in one direction, I decided to go in the other because we couldn't all go in this particular direction, and it's it's it's been like that ever since I went through high school in Denmark where my class wanted to become engineers, and while I was interested in it, I couldn't feel like, you know, we all should do that, so I had to do something else. Personally, I don't I don't have a background in my family at all within, sophisticated research. Nobody in my family had an advanced degree. I didn't know what what that would entail, but the doors opened. I come from Denmark, and it's really advanced society today, but I'm still the 1st generation from a family that sort of came out of the farming generation. And the doors opened for me because of of of the free education and the system was there.

 

Jan Jensen (Trailhead Biosystems) [00:04:23]:
And I was a kid that just enjoyed sort of mathematics and physics, but never even thought about daring to jump into something as crazy as science. So I, coming from a military family too, my father was in the military for his entire life, and I wanted to be more or less a fighter pilot, but I couldn't because of my eyesight, I ended up eventually within the University of Copenhagen. And that was back in the early '90s. And then I somehow realized that because I decided on biochemistry. And biochemistry was because it was not engineering and maybe I could do research if I became a biochemist, but I really had no idea. So I threw myself at biochemistry and realized then that the more effort I put into this, the better I became. So it all one step took another. I went from biochemistry.

 

Jan Jensen (Trailhead Biosystems) [00:05:23]:
I went into molecular biology. And then after a couple of years in that, I then realized that this thing called cell differentiation, that's what my heart was actually beating for because it was so complicated and we didn't really know what controlled it. At that time, we had just begun to find the first genes. There were some fantastic papers and there were some distinguished scientists in the United States and I saw a presentation by Bob Tietjen from Berkeley, came to Copenhagen, gave a presentation. I was blown away of how sophisticated that type of science was. So I was more or less just this is this is what it's gotta be. So I threw myself and attempted to become a researcher and did a PhD focusing on these transcription factors that are controlling genes. And I was fortunate to to actually do this in a very large company, in Novo Nordisk.

 

Jan Jensen (Trailhead Biosystems) [00:06:22]:
While I was still getting the degree at University of Copenhagen, I could still do it at this fantastically endowed research institute that was owned by Novo Nordisk. It was called the Hagedorn Research Institute and and with that name actually came one of the, renowned diabetes research institutes in the world. And, I did not know really what it was I was finding myself in, but by happenstance, my interest in cell differentiation landed me right in the middle of the field of diabetes. So that's where it started.

 

Jeffrey Stern [00:06:55]:
Wow.

 

Jan Jensen (Trailhead Biosystems) [00:06:56]:
And since then, I've just been moving through life as a scientist mainly focused on curing diabetes, which is also part of the reason that Trellid exists, which we can talk about. But, yes, it sort of became a happenstance role of an emerging scientist that just wanted to see what was behind that door that I didn't even know existed.

 

Jeffrey Stern [00:07:18]:
That's amazing. I I think I feel like I'm gonna have to ask a bunch of clarifying questions given the nature of of the topic that we're discussing here and the the complexity of it. But just to kinda set a baseline, what what is cell differentiation?

 

Jan Jensen (Trailhead Biosystems) [00:07:32]:
Yeah. So if we look at ourselves, we consist of cells. Most people know that. And there's a couple of trillion cells in our bodies, but there's not that many different types. Altogether, we have around 500 or so different cell types. So for instance, if you're looking to your liver, the cell type that's most, prevalent there is called the hepatocyte. That's the cell that does most of the workload of the liver. But there are some other cells too.

 

Jan Jensen (Trailhead Biosystems) [00:08:00]:
There's some that are called cholangiocytes and they're the ones that collect the bile into the gallbladder. And you have got endothelial cells that provide the blood vessels for the liver too. And there are more cells. So without going into detail of how many cells that may exist in the liver, each organ consists of a different set of types of cells. Now cell differentiation is essentially the process by which cells become different. They're in the name. And then then what what what the heck does that mean? I mean and now you have to think about where we actually come from. Our very first existence happens at fertilization.

 

Jan Jensen (Trailhead Biosystems) [00:08:42]:
Thank our mother and father for that event. But after that, we're sort of a little bit on our own initially, of course, in the uterus. And it's a beautiful thing, this thing called life actually from a biological standpoint also from everything else, but it's pretty fascinating what happens after fertilization because, that cell, that oocyte that now got fertilized, which now consists or has all the biological information that it needs, encoded in the genome to create something as complex as we are as we speak here today. Is essentially that's where cell differentiation comes in and and is is essentially explaining how all of these cells became different and also numerous. So in the embryo, which we now refer to it, I mean is a is is a process of cell proliferation and then sometimes cell specialization. And the specialization is what we call differentiation. So all of a sudden, there is a change inside that growing embryo that is now not homogeneous anymore but it begins to from the outside, actually we can see patterns emerging. We can see that the riches coming where the brain would be, and it emerges into the process of what's called gastrulation which is the first true visible evidence that there's something really complex being formed here, our organism.

 

Jan Jensen (Trailhead Biosystems) [00:10:10]:
And when that process happens, this is a simple this is like an orchestra playing all at the same time. It's it's beautiful. All that information that's been packaged into the genome over the 1000000 of years that has led to where we are today as a species is now being interpreted and is being interpreted in space and in time. So as the embryo grows, it gets larger and larger because there are more and more cells. And the patterns and in development of biology, we refer to it as patterns because we can see these changes in gene expression and emerging structures of the embryo that is now being created. This is this is governed entirely by the genome and how the genome is being interpreted. So if for instance, one field of cells becomes specialized or differentiated, it will now begin to signal to others so that they also can become differentiated. And therefore, it's actually a process where the cells in the embryo communicate with each other all the time as they help each other to specialize.

 

Jan Jensen (Trailhead Biosystems) [00:11:23]:
And in developmental biology which is a field that I learned, we call this process, we call it vertebrate regulative development and it means that the cells are communicating. There's not a single cell in the embryo that is given its ultimate destination from the outset. They can all in a very plastic way communicate and then build the robustness up of that eventually creates us as an organism. One example I can give you is for instance, our developing limbs, say the arms. Sure. They look very similar if you look at the right. If you look at the left, it's like they're mirror images of each other. All that information that was encoded to build them was in the genome that was interpreted in interpreted in 2 different fields.

 

Jan Jensen (Trailhead Biosystems) [00:12:12]:
1 on the left side and 1 on the right side of, the embryo. And they never communicated to each other, so the left arm, the information there was not traveling over to the other to say you should be a little longer or something like that. No. The process here is entirely interpreted within the field from which there arose. So it just speaks about the how strict the rules are followed in the normal embryo. And I think as a biologist, it's like this is where I find comfort. I find comfort in the strength of biology because it works really, really well If if you're not messing it up by putting it into sort of an artifactual environment as a cell culture incubator is or a bioreactor, This is not the normal environment, and therefore, the cells behave very differently. And that's one of the challenges we have in the field.

 

Jan Jensen (Trailhead Biosystems) [00:13:07]:
But the embryo itself, that's the safe harbor. That's where the process of differentiation occurs unperturbed and well.

 

Jeffrey Stern [00:13:16]:
Fascinating overview. Thank you for that.

 

Jan Jensen (Trailhead Biosystems) [00:13:18]:
There's a little lecture in developmental biology, but new people actually ever hear it. And I think it's a story worth telling because we all went through

 

Jeffrey Stern [00:13:28]:
it. Right. No, of course. So where does your path and interest in cell differentiation and developmental biology converge with your presence here in in Cleveland?

 

Jan Jensen (Trailhead Biosystems) [00:13:40]:
So that's also happenstance. So you see I I as I said I landed in the in the pancreatic field because the pancreas is is the organ in which the pancreatic insulin producing cells reside. And my first research back in Denmark was actually focused on where do these pancreatic islet cells come from because some investigators thought that they came from what's called the neuroectoderm. And I I just couldn't come to grips with that as a scientist because when I looked at the embryo, it didn't look like that. So so most of most of my first research was actually trying to sort of help in the understanding of, you know, no. The these cells are from the pancreas. They are formed within the pancreas. And, so so I was spending most of my early career studying the very very basic science of this formative process of a cell that produces insulin.

 

Jan Jensen (Trailhead Biosystems) [00:14:36]:
Now those years were in the in the nineties. And from a scientist perspective, it was quite successful because I managed to publish some publications that then led to the capability that I could move on to the next stage in my career. And that then was a question that was given to me strangely enough by a German that was participating in a conference in a Swiss resort. A beautiful Swiss Alps, and he asked me because he was a professor at University of Pennsylvania, and he said, Hey, Jan. What do you think about coming to the United States and becoming a researcher? I had no idea what that would mean. So I said, tell me more about it. Well, you know, it's If you become an independent researcher, you will get some grants, some support, and you can decide what you wanna do. And I felt that was unbelievably fascinating to think about because I wasn't really geared up for a university career in Denmark, I thought.

 

Jan Jensen (Trailhead Biosystems) [00:15:37]:
So I managed to convince my girlfriend, now wife at the time, Sine, was it okay if I was sort of for a little while thinking about perhaps going to the United States? She said, Okay, but only for 5 years. Thank you very much. So back in 2,001, I applied at the University of Colorado for a position as a researcher as a young faculty at that university, and I got the position and then I moved almost immediately. And then I was at what's called the Barbara Davis Center For Childhood Diabetes, which was a very good, still is, institution in the US focused on diabetes. And so I spent a couple of years there, actually almost 7, to build a laboratory up, and I was focusing on development of the pancreas and the islet cells, so I continued that research. Thank you very much to the American Diabetes Association for providing the early funding for that. But after a couple of years, after having established the lab, I received a letter from here in Cleveland. There was this strange institution I actually did not know too much about, I have to admit.

 

Jan Jensen (Trailhead Biosystems) [00:16:43]:
It was called the Cleveland Clinic. The name had had sort of, I heard about it before.

 

Jeffrey Stern [00:16:49]:
Sure. Small small system.

 

Jan Jensen (Trailhead Biosystems) [00:16:51]:
Yeah. Well, it was mainly because I didn't really know much about diabetes research in Cleveland and there was not too much going on. And now of course there was a good amount of of maybe clinical research, but basic research was not too much. So there was an interest in seeing if, that could be started up here, and and I got convinced, you know, that that was a good idea. So I moved to Cleveland and and and became, a staff at at at at Cleveland Clinic. And I was there for a total of, I guess, 13 years before I moved here to Trailhead. And therefore, I could continue the laboratory and perform studies on the same subject matter, which is how does a pancreatic beta cell develop and can we cure diabetes. So that's what took me to Cleveland.

 

Jan Jensen (Trailhead Biosystems) [00:17:37]:
And the 5 years that my wife said we could be in the US, quickly turned into to 22 and, and going. And and now it's Cleveland, and, this is the place we call home.

 

Jeffrey Stern [00:17:50]:
So how then do you bridge this gap from research to to entrepreneurship? And and as you think about, you know, Trailhead Biosystems and the work you're doing now, what was the founding story there? What what were the questions you were asking? What did you have a vision for the kind of work you would be you would be doing now?

 

Jan Jensen (Trailhead Biosystems) [00:18:10]:
Yeah. I think the vision has always been there, but to convert it into reality in research means how do you find funds to do that? And and that's hard in the academic world. It's very, very challenging, actually. And that's just how the system is built in general. Back in 2011, the idea to, create a company here in Cleveland based on the technology that we were developing at the clinic was fostering the thoughts about Yeah. Let's let's see if we can build a company around this and then add another technology that would then be contributed by another company actually outside the country. So so there was a good amount of effort in that phase between 2011 to 12 in attempting to actually create a diabetes oriented company addressing the disease curatively. But it it never actually came to fruition.

 

Jan Jensen (Trailhead Biosystems) [00:19:02]:
And after it's it's it's that happened, of course, there was a bit of frustration because there's a lot of effort that was put into this. But the idea never left. And the State of Ohio by virtue of the JobsOhio program and the Ohio Third Frontier actually had a a program going, then. It doesn't have it anymore. Sort of a pity because it was a good one, but it was called the innovative platform program. There's quite a good amount of funding in in the lower single digit of 1,000,000, but more than a few $100,000. And the idea that I had that we would use in that previous idea for a company in order to create a machine enabled system that can investigate and understand cell differentiation. That was baked into a proposal that was submitted back in 2013.

 

Jan Jensen (Trailhead Biosystems) [00:19:57]:
And that was submitted through the Case Western Reserve University even if as I was at the Cleveland Clinic. So it's sort of a partnership application. And then there were several commercial partners that's also participated in it. Now that was actually awarded, and we termed that Ohio Alive. So it was part of the regenerative medicine focus that the state has been focusing on for quite a number of years. And so, therefore, it started through this program and but I still remained at the clinic and then was sort of, by the state of Ohio, put on the path of creating a company. And so that's what happened because Ohio Life became Charlotte Biosystems in 2015. And then since then, took me on the entrepreneurial journey to build value, growth, and products.

 

Jan Jensen (Trailhead Biosystems) [00:20:46]:
Initially, it was built on services, and that wasn't a good idea. So we had to change that, path, of doing business. And since then, we have changed and focused on making sales, for many particular different uses that we can talk about.

 

Jeffrey Stern [00:21:04]:
Yeah. I definitely wanna explore those use cases, the implications of it, the nature of the work you're doing. One question I wanna ask though, it's it's one of the perennial startup questions, which is why now. But I'm I'm curious particularly in your context, like, what technologies now exist across developmental biology, stem cells, hardware instrumentation, computation, like what is allowing for you to do effective cell development and in a commercialized, you know, capacity?

 

Jan Jensen (Trailhead Biosystems) [00:21:39]:
I mean, Trailhead is continuous developing and increasing armament of technologies around a core technology that we call high dimensional design of experiments. Now, this technology is not the only one that exists that can help in addressing this problem of cell differentiation. That's for sure. So it's a good question that you ask. Most of the other technologies that are being developed alongside what we're doing are to a large extent descriptive. The whole field of developmental biology has for decades. Its entire existence has been a descriptive way of science. You look at the embryo, you see what's happening and then you talk about what you see.

 

Jan Jensen (Trailhead Biosystems) [00:22:25]:
With the advent of gene editing, the knockout technologies, it was possible to go in and eliminate a single gene or 2 in a developing mouse and then you can ask a question, well, what happens if you don't have this component? But aside from that, and that was not human, by the way. That was only in the mouse system or other organisms. So it has been hard over the years to perform experiments where you're at a very large degree change the system where you change the parameters and look for an outcome. The field of what's called systems biology is is essentially stating that this is what you need to do in or in order to understand biology because it's the biology is so intricately wired with the genes communicating with genes. And as there are thousands of genes, and it didn't come with a blueprint, how can we, going in one gene at a time, ever begin to fully understand this system that consist that we consist of? It's just impossible. So I guess that was the motivation I had is to to build a method that can, in a very powerful way, not just play one string on the violin, but essentially have multiple instruments in play at the same time so that we can sort of listen to the tune. And this is this is how high dimensional perturbation works. You you select a couple of instruments that you then play, but you really have no idea what you're going to listen to.

 

Jan Jensen (Trailhead Biosystems) [00:24:02]:
But you're going to attempt to listen to things that you know should be important in cell differentiation, so that's what we do. You can't take anybody to just, you know there has to be a certain understanding of developmental biology before you do these experiments. But together with the machine enablement and what we do, we we we quite effectively now, I think at least, we quite effectively extract some critical what we call critical process parameters. And that, by the way, is the term that a process engineer that uses DOE design of experiments uses in order to gain process understanding. And so if you wanna capture where Trailhead is located, we are located right at the engineering interface to biology, and and that is where we employ engineering methodologies, but at a sufficiently high gearing to address biological questions, especially that of control of sulfate. And and we get we we are just focusing on getting better and better every day. And since we've been at it for for several years now, it's almost becoming a systematic approach for us where we where we get, yeah, we get better, for every experiment that we do because they all speak to each other.

 

Jeffrey Stern [00:25:21]:
I I think it it might be helpful to perhaps walk through an example of what this looks like in practice, and you maybe diabetes is is a good one to Yeah. Work through, but what does this actually look like in in practice?

 

Jan Jensen (Trailhead Biosystems) [00:25:39]:
So so let's let's let's first start with the material that we may start with. Right? The stem cells. It's such an, you know, many people are ethically concerned and so forth. But we're not using any embryonic stem cells here. We're working on induced pluripotent stem cells which are coming from adult organisms. And they are capable of being reprogrammed, as it's called, through a process where one can overexpress a certain set of gene regulatory factors. When that happens, then they return to a state that's very, very similar to that of the early embryo. And at that point, they can expand and grow essentially indefinitely.

 

Jan Jensen (Trailhead Biosystems) [00:26:20]:
They also have the capability to become any other cell type of that I just spoke about, all the specialized cells like a hepatocyte or a pancreatic beta cell. But that process is one that usually is done only in the context of an embryo, and the embryo is not present here. So how do we do it without the embryo to help? We have to do it in a dish or in a bioreactor. So what we're seeking to do is to guide these pluripotent stem cells one step at a time forward so it ultimately become the cell we need. And we have to do that just like it would happen in the embryo. So for instance, if you we call it multistage differentiation. The first cell you're gonna make is, for instance, if you wanna build the pancreas, is an endodermal cell cell. That's what's called the germ layer from which the pancreas comes from.

 

Jan Jensen (Trailhead Biosystems) [00:27:11]:
After you do that, you then generate a field within the endoderm. So you avoid making a liver. Avoid making a lung because that would be alternatives. And then, you make the pancreas instead. When you now reach the pancreas, it's like driving to Chicago from here. Right? You wanna hit Toledo first, hopefully, because if you end up in Pittsburgh, you're in the wrong direction.

 

Jeffrey Stern [00:27:31]:
Right.

 

Jan Jensen (Trailhead Biosystems) [00:27:32]:
Right? So so we we we're gonna drive to Chicago through the sales stages here, and we're gonna go through Indiana at some point. But first, we gotta go through Toledo, and then we continue west. So so here, the first one was pancreas, endoderm and then pancreas. Then we create a pancreatic endocrine cell. And then the endocrine cell has to be a pancreatic insulin producing cell and not some other pancreatic endocrine cell. So you see, at every single step that we employ the technology, we're trying to get further and further specialization to that destination, so we finally end up, in the place we want to be at. And and this is the same process we need to follow for making a liver or a cell in the brain. It's just a different destination.

 

Jan Jensen (Trailhead Biosystems) [00:28:21]:
And that's how to look at it. And if you look at the logo for Trelegette Biosystems, you can see in that logo exactly what I just said. You have like a GPS needle, and that's indicates, waypoint finding. These are the coordinate sets, but we're we're moving from a platform to another platform to another platform, and there are 5 platforms in total. And that indicates the cell stage that we move this needle over from stage to stage. So essentially, the process of HDDOE is the one where we build a protocol up that is hopefully sufficiently good in order to make a good conversion into the sales state that we want.

 

Jeffrey Stern [00:29:08]:
Okay. That is also very helpful. So to to help me understand, here some of the the implications from a business perspective. Yes. What is it that you are are selling?

 

Jan Jensen (Trailhead Biosystems) [00:29:19]:
So we we would like to be actually the leading supplier of specialized human cells. As there is quite a good number of these and there is also quite a good number of different ways you can use such cells, We're not really in lack of an opportunity or market. So if you think about it, consider these cells as sort of Lego blocks. They come in different colors, and they come in different shapes. They can be used to build different things. So for instance, if if you own a 3 d bioprinter, and there are several companies that make those, and you wanna fill it up with material to print, then some of that material needs to be living cells. If you if you wanna build a skin, you gotta have some skin cells to print. If you wanna build a liver, you gotta have some liver cells to print.

 

Jan Jensen (Trailhead Biosystems) [00:30:08]:
And if the ink is dirty, say if the cell is not pure or not functioning, it's almost unimaginable that you can print something that's worth putting into patients or study because it's affected by the poor quality of cells. So therefore, there is a strong need for better cells for say, 3 d printing. But now assume that you, for instance, in the field of, say, you wanna make a new drug discovery for Parkinson's disease. Okay? And there's a good need for that. How do you do that? Well, you need to perform what's called a drug screen. So you probably have what's called a library of very small molecules, drugs by the 1,000, synthesized at a very large cost by some organic chemists or peptide chemists out there. But you need to run the assay where you can see, can you actually find this drug that might be affecting a cell state so you can predict that you can, say, improve in Parkinson's disease. So to do that, you're actually in need for what's called midbrain dopaminergic cells, dopaminergic neurons because these are the cells that are affected and dying in Parkinson's disease.

 

Jan Jensen (Trailhead Biosystems) [00:31:23]:
So as as we have built a protocol, a new protocol for these things called a 9 midbrain dopaminergic neurons, We then want to offer these, to drug discoverers, pharmaceutical companies to be used in drug screens so that they can get a better hit than any other assay that they could imagine doing. Because if you can't get these cells out of a human brain, it's impossible. And you might be able to do it on some half cooked mouse cell, but then it's a mouse test. And ideally, you wanna do it in a human cell in the right context, and you can either even make these cells so that they mimic, say, human Parkinson's disease through genetic editing. So in other words, the cells can be used as tools for 3 d printing or for studying human diseases or for drug discovery. And we haven't even yet begun to talk about therapeutic use. Because the therapeutic use always sits there and people think that that's what you can use the cells for. That what can you do with these dopaminergic neurons? Well, they can likely cure Parkinson's disease.

 

Jan Jensen (Trailhead Biosystems) [00:32:36]:
And if they're the right cell, provided at the right amount in the right location in the brain. And there is a company called, BlueRock right now, owned by Bayer, a large pharmaceutical company. And they have gotten approval for a clinical trial of their dopaminergic neurons, and they're recruiting patients right now. I just saw the news report from a Danish Swedish alliance that have also gotten approval to test. So the therapeutic approaches using stem cell derived cells is now coming, and it will change medicine. And I think Trelec's role is to simply develop the best cells and also seek that our cells become tested, for therapeutics. And to do that, we're looking to partner. So, we would discuss with companies that are interested in developing partnerships for clinical therapy.

 

Jeffrey Stern [00:33:36]:
Wow. That that's extraordinary. The implications, you know, are are incredible with with that work.

 

Jan Jensen (Trailhead Biosystems) [00:33:44]:
Well, I mean, there is still just remember, there's not a single therapy based on iPS cells that has been approved. So we're still waiting the first win. And if you look at the the diseases that that for which if you have the cells that can possibly be cured using stem cell derived specialized cells. There are actually quite a number. But the top hitters are, for instance, diabetes, type 1 diabetes. We need pancreatic insulin producing cells at scale to do that. And that's where the current trial that's the furthest ahead is ran by a company called Vertex in Boston. They bought a company called Sema, also from Boston, and have, now, gotten the first patients, fully off insulin or close to fully off insulin as far as I know, in in in their trial using stem cell derived insulin producing cells.

 

Jan Jensen (Trailhead Biosystems) [00:34:39]:
So there there are multiple companies that are interested in seeing successes in this space. And I hope that because this is what brought me into this space initially is the hope that, we can we can get beyond insulin treatment but move into curing people instead. Why do we have to inject every single day? Why do we have to be worried? Why do we have to have these complications? All the problems associated, say, living with diabetes for a lifetime when the cure is so obvious, just put new cells in. It has been the thing that has always driven me, the simplicity of addressing that is there, but the complexity of making the cell has always been the thing that has followed.

 

Jeffrey Stern [00:35:31]:
So so Trailhead then really revolves around this combination of producing the biological building blocks, you know, the purity of the the Yeah. Cellular ink, if you will, you know, the the the printing ink and some kind of experimentation around, you know, how that can be used for drug discovery therapeutics, like you mentioned, not yet, but perhaps in the future and and understanding disease. Is that a a fair summary?

 

Jan Jensen (Trailhead Biosystems) [00:36:00]:
That that's a fair summary. There's still even further applications of cells, but but what we talked about here are are by far the the the most important areas of engagement. And what what can you say? It's it's a one of our problems is to find out what direction we should go, not where we could go because it's there's so many cells that we can make. The technology that we have is is strong enough to likely succeed in making any cell what that we said are a foot forward to make. But does that mean it's a cell we should make now? So what what Because there there's not an unlimited amount of resources available. Right? Now, we need to focus to create a sustainable business model and and and and grow through that, understand how to get to a market, and understand how these markets operate because many of them haven't been served at all. And we need to understand what customers and partners are looking for, in the sales that we deliver without messing up too much along that way. And so, therefore, it's a it's a constant sort of testing forward, getting out there, asking, and meeting people.

 

Jan Jensen (Trailhead Biosystems) [00:37:23]:
Cleveland is not Boston. It is not San Francisco and it's not San Diego. So we are not in the wheelhouse of of our ecosystem of biotech in general. So most of what I'm talking about here has to happen both nationally and internationally outside that of Cleveland. It's and that's just one of the challenges we have to deal with.

 

Jeffrey Stern [00:37:49]:
I I know you have raised around $10,000,000 towards this effort. Maybe just kind of give us an overview of what the the company looks like today and where, you know, where your traction and and focus is as you are trying to parse where should you go versus where could you go?

 

Jan Jensen (Trailhead Biosystems) [00:38:06]:
I I think so what we figured out is that where we should go is make some sales and sell these, and get a revenue basis in this space because it's entirely doable. Then all the therapy comes automatically, for her on on on that basis because they're also there. They're not gonna go away, and we'll find paths for that. So we are focused on production, and we have raised into creating a better set of capabilities into making the cells, growing the cells, scaling them, and hiring in on sales. And then we have we've decided to stay here in Cleveland. We we were able to purchase a facility that we're gonna move into actually in in in not more than a couple of weeks.

 

Jeffrey Stern [00:38:56]:
Oh, wow. It's

 

Jan Jensen (Trailhead Biosystems) [00:38:56]:
located in Beechwood. We have fitted out a reasonably well sized lab space, a tissue culture facility, some manufacturing area, bioinformatics, employee lounge and offices out there so that we can grow in our own space. And I'm just looking forward to that because, it it'll be a new, it'll be a new phase of the company, and it's a little bit overdue, I would say.

 

Jeffrey Stern [00:39:24]:
Oh, that's that's very exciting. What is like the next thing that you have to to validate, as part of this journey? And I guess a different way to ask that is in retrospect, assuming you achieve success. I guess, one, what what does success look like? And what are the the steps along that that journey?

 

Jan Jensen (Trailhead Biosystems) [00:39:46]:
I mean, most people think about success as being some point in the future where, say, a revenue milestone has been achieved or an acquisition or an IPO and so, and they're all sort of meaningful demarcations along the way, but to me, you know, what I what I see when I go to work every day with with the team that we have here and and how much that's happening, how much people are growing, and the type of of of understanding that we get just from our activities, that's success. The lapse in the lab and just seeing a company being built is success. Yes, there are some other defined milestones that we're gonna put up and we will and we have to because that's how you have to work in a start up company because those deliverables are key. But in and of themselves, they're not they shouldn't be the success milestones because there's a lot of things that are unexpected and it happens. And, that can, if not more, impact the success criteria. And finally, as a scientist, I have to admit that science never moves in sort of the fully predicted way. Right? Usually, there are some events that just stand out as being transformative. I think the first for us, the first transformative event was when we did the first large experiment that we could actually see.

 

Jan Jensen (Trailhead Biosystems) [00:41:21]:
And that's many years ago now, but at that point, I just knew. So when you combine value building and science, it gets risky because science can take forever. Scientists think that they can be at it forever. Companies have a, you know, limited amount of time to focus on creating particular milestones are of commercial interest. So how do you how how do you create the pickup of the value of a scientific process? I don't have the full answer to that, except to say that I'm I'm I'm believing that we have to we have to gear up that science to really deliver, and then we keep the scientists extremely focused so that they don't get too much into another rabbit hole and and and lose that focus, which is all too easy. We have a little bit of a motto here actually, and from a reflection standpoint, so it's it's we change the scientific process. And that's a big statement to state that because you can't change the scientific process. Right? It just is what it is.

 

Jan Jensen (Trailhead Biosystems) [00:42:30]:
But if I try to explain why I'm saying something like that Mhmm. It's because all the scientists that we're essentially training, teaching them how to get grants, teaching them how to do experiments, is all based on hypothesis driven research. And hypothesis driven research is by definition then rooted in the human mind of a hypothesis. You come up gotta come up with an idea. And then by virtue of your training, you will test this idea to either prove it or show that it is a false. And that can take a good amount of time to do, and you buy into this idea of yours. So you might get cognitively biased towards what you want to see. But the biggest problem is that this is human centric process.

 

Jan Jensen (Trailhead Biosystems) [00:43:17]:
I I call that the anthropocentric problem here. Anthropocentrism essentially just means that we we tend to to view ourselves as superior as a species. And you can see that in so many different things in society where we're the apex species and so forth. Right? Mhmm. But in science, it also means that we tend to think that it takes the Einstein, to understand the world we live in because it's the most intelligent mind that can do that. But to me, I mean the biology world that we're entering into here is so highly dimensional that the human brain is incapable of assembling that. It cannot be done. So in other words, what can we do to sort of take the human out of this process and let the machines help us So that we will amplify the experimental interrogation.

 

Jan Jensen (Trailhead Biosystems) [00:44:16]:
In other words, try to avoid thinking about all the hypotheses. Don't do that. Just test your way through. Get the response back and listen to what nature just told you. And this is sort of that the other perspective to this is to see are you aren't you yourself the biggest roadblock? And I think that's what dawned on me back in 2011 that I was beginning to realize despite all all the years I've spent as a development biologist that I simply wasn't capable of doing this. No matter how much I would spend time, years hiring people, publishing papers, we're not gonna get through this problem. And, still with whatever we have, what we're applying here, these are sophisticated problematics that we're going through, but it's a lot better than what it was before when you could test ideas 1 at a time. So, yeah, changing the scientific process just means that we're sort of trying to make ourselves a little bit smaller, help it with the machines.

 

Jan Jensen (Trailhead Biosystems) [00:45:22]:
One example I can say is that that everybody can sort of realize or relate to is, take 2 people. Give them a task. It's the same task. Dig a hole. Okay? You can go find the strongest person on earth you can find a Schwarzenegger style. Okay? Sure. Could you go dig your hole over to the left and then I'll go find the little weakling over in the other side, and then I give him the excavator. Okay.

 

Jan Jensen (Trailhead Biosystems) [00:45:47]:
And then we'll come back tomorrow and see who dig who who was digging the biggest hole. It's the same thing. Right? It it it doesn't take physical strength. It doesn't take mental technologies that you're talking about that could that are involved here, they are all talking about that could that are involved here, they are all helping us do more as scientists. But I'm mainly focused on what's called the empiricist side, the the experimentalist side, those that actually do the experiment, not those that gather a lot of data and try to make sense of what they looked at. Can compare to the physicist, you can have a theoretical physicist, or you can have a physicist at CERN that runs a particle accelerator. Mhmm. I like to be the person with the accelerator, not the one only theorizing.

 

Jan Jensen (Trailhead Biosystems) [00:46:41]:
Because eventually, you do need the data to understand whether or not your theory was correct or not.

 

Jeffrey Stern [00:46:49]:
No. I think it makes a lot of sense that building a company is is one of the more effective ways to test the efficacy of of those ideas. How optimistic are you that and in what time scale that, you know, some of these challenges that, you know, humans face biologically could be solved?

 

Jan Jensen (Trailhead Biosystems) [00:47:11]:
That's the question you should never ask a scientist because if the if the scientist comes back with the time frame, you know, he's completely bunkers. So so I've always learned never ever to put years on anything when it comes to when do we have the cure. And so many years ago, I was hoping that the cure for diabetes would happened at the the century of the discovery of insulin, and that would have been last year because insulin was discovered in 1921. But that didn't happen, so we're still a couple of years behind, but I was hoping that it could have happened. But I think the proof of concept has been shown. It's just not approved as a medical therapy yet. So it will come, but I'm not the one to say when. I just don't dare.

 

Jan Jensen (Trailhead Biosystems) [00:47:59]:
I think, I mean, because most of these from a therapeutic perspective, as you're very aware, takes years of regulatory, fighting to get and testing, to to to get new therapies approved, but they will come. There's no question about it. They will absolutely be here. But when they will be here, whether it's a decade out, maybe even before for some, or whether we have to wait 2 decades. And what I can say is that the the process of development now is exponentially accelerating. Right? Mhmm. So what what was happening over 1 year, say 10 years ago, probably now happens within a month or so. I'm I'm speculating there.

 

Jan Jensen (Trailhead Biosystems) [00:48:46]:
I can't say for sure. It also depends on what you're looking at, but it's very clear that we can move faster now than we ever could, and I expect that acceleration to continue. I don't know if there is a Moore's law on on the scientific side, but it's the same principle.

 

Jeffrey Stern [00:49:05]:
Yeah. What what has surprised you most about your journey so far?

 

Jan Jensen (Trailhead Biosystems) [00:49:11]:
I don't really know. You you got me on that one. Let let me let me think a little bit about that.

 

Jeffrey Stern [00:49:18]:
Sure. Yeah.

 

Jan Jensen (Trailhead Biosystems) [00:49:20]:
Yeah. I think what has surprised me is that you know usually the worst outcome that you think in a given situation later can turn out to be one of the best. And you had no idea that, you know, that is the failed attempt to make a diabetes company that led to Trailhead. It was wonderful the first one failed because it would never have had the opportunity that this one has, I think. There are there are the I mean, I'm very happy that I don't have the perfect eyesight because had I been a fighter pilot as I wanted to, I would have been, ferrying some people in an Airbus or something like that today or or whatever. Right? I mean you just don't know. So these events in life that you think are setting you back are more often than not just throwing you forward. You just don't know it, and and But you have to get forward, and then you begin to reflect on, oh, oh.

 

Jan Jensen (Trailhead Biosystems) [00:50:20]:
And and and and then so I've just learned to accept fate. So if there's something that doesn't go my way right now, I say, well, maybe it's not meant to be. So we'll see what then comes. We can do the best in the moment that we are and put our integrity forward, trust in our ability to change, and then lean on others. Right? I mean Trailhead is not me. I have to say that. It's the idea perhaps but it's the team. I mean honestly, I'm not doing this science.

 

Jan Jensen (Trailhead Biosystems) [00:50:52]:
You have to interview the folks that are actually doing the experiments that are in our company now. So and if Trello becomes successful, it's also not because of me, it's because of the team 100%. And I'm totally in awe of how such a collective can form, and that's why I love the word company. It's the right word. Where I come from, we don't call it that when you when you build a company. We call it something different when directly translated, but the word company is a great name because it's a company of people. And as much as we talk about technology here, it's absolutely a dead thing. Technology doesn't do anything.

 

Jan Jensen (Trailhead Biosystems) [00:51:34]:
It is when the humans come in and use it that there is an impact. And this the value of a company lies in its employees. That then can be amplified with technology but it's always the employees. And I could just call it the team. So I'm I'm just So there you go, you know, going back to the success thing. If you're able to go to work and you surround yourself with unbelievably gifted individuals, that's success. Mhmm. I

 

Jeffrey Stern [00:52:03]:
love that. That's awesome.

 

Jan Jensen (Trailhead Biosystems) [00:52:05]:
To me, at least.

 

Jeffrey Stern [00:52:08]:
Well, tie into our our closing question here, which which we ask, everyone on on the show, which is completely unrelated to the work you're doing. But it's for your favorite hidden gem in Cleveland.

 

Jan Jensen (Trailhead Biosystems) [00:52:23]:
Yeah, so one can think about, oh it's a walk in the park out in metro parks. Oh, is this the place to go for the best sandwich or stuff? But I don't know. I think I actually think the hidden gem in Cleveland is Cleveland. To me, it was off the radar. It was flyover territory in diabetes. I think we've been successful here because we're in Cleveland sort of hidden. I don't wanna be condescending about this, but we don't really It's very difficult to think about a large number of biotechs in Cleveland, and I think it's been good for for this little company here because, you see that sometimes you know they're venture capitalists. They wanna start a company and set aside funds, and then they found a cracker check team, and and and and then they say they're all in stealth because they don't wanna let anybody know what the heck they're doing up until the point when they come out of stealth, and then the world can see how much of a great idea that they've been now working on collectively for a year.

 

Jan Jensen (Trailhead Biosystems) [00:53:30]:
I mean, Trello has never been in stealth, but we've been in Cleveland. And it's been working fine because we've been we got the time. We got the support. There's a lot of buy in in the state of Ohio to what we're doing, and I've just been, you know, one can say that the area that we're in fits in what is referred to as deep tech, deep technology, and it just takes time to learn this stuff. Right? We're doing things in a new way. You're gonna make a lot of mistakes, but you learn, but you need time and I think we got time. We got early support and now, we just need to prove that we can make an impact, and that impact is by delivering material. It's not our technology because the technology doesn't matter to anybody unless we can provide cells.

 

Jan Jensen (Trailhead Biosystems) [00:54:26]:
So and and if if so there's there's there's a market strategy. There's a production strategy. There will be a lot of learned principles along that that we have to go through. I think we can solve that, I hope. But so so there you go. I mean, the the transitions are are natural. And and Cleveland to me grows on you. I mean, raising a family in Cleveland is not a bad place to raise a family.

 

Jan Jensen (Trailhead Biosystems) [00:54:52]:
That's why we're still here. I think that Cleveland has a great opportunity to attract all the biotechs out of Boston, out of San Diego, into Cleveland. It's not just the cost of living. It's not just the cost of lab space. It's a it's a good place, to do it. Most of the employees we get here, we can find in Cleveland. Mhmm. Some on the more senior side, we have to look out of state for just because, it is.

 

Jan Jensen (Trailhead Biosystems) [00:55:23]:
And and there is a general excitement and also a very down to earth attitude to how to get stuff done here. One of the things that strikes me as important is so I've I've been talking to several people in the Silicon Valley, and, you know, the entrepreneurial mindset is is is flowing through the veins of everybody out there. Yeah. And it can take you into the air and, you know, all of these could be's are then, and you get dizzy. You get really dizzy. So what what is all of this? Is it all make believe and so forth. Right? And most of it is by and large just speculation. And for sure, they showed the world how to, you know, build technology companies.

 

Jan Jensen (Trailhead Biosystems) [00:56:19]:
But but the mind cell itself is is is is just causing confusion. I mean to me, it causes confusion. Coming back to Cleveland, you're grounded again. Here, you are grounded. You know, you're it's it's you can focus. And and and that's what is also something that I think is important that we can very very quickly get distracted. And we don't necessarily need all the noise, but now we need to make some noise. Now we need to get out and talk about what we can do, So we have to turn it around a little bit.

 

Jeffrey Stern [00:56:49]:
No, I love that. Cleveland as the meta hidden gem of Cleveland.

 

Jan Jensen (Trailhead Biosystems) [00:56:53]:
I think many Clevelanders would probably think like that because it's yeah. We all know the statements of mistake on the lake and whatever. But but then again, people still stay, and many are loving coming back. So I like to see Cleveland in in in 10, 20 years, hopefully continue along the trajectory that has put itself on. There's still a lot of work to do, I would say. I'm not fond of letting urban blights stand, and let's just face it, we have that. Where I come from in Europe, such is just not tolerated and will be fixed, but then I can say what I've seen over the last 10, 15 years has been remarkable, and I just hope we can continue to do that. But we have to do it together, and we have to trust each other.

 

Jeffrey Stern [00:57:46]:
Well, yeah, and I really appreciate you coming on for sharing your story, your perspective. It is fascinating, inspiring work. So thank you very much.

 

Jan Jensen (Trailhead Biosystems) [00:57:55]:
Thank you so much, Jeffrey. Such a pleasure being here.

 

Jeffrey Stern [00:57:58]:
If, if folks had anything they wanted to follow-up with you about, what would be the the best way for them to do so?

 

Jan Jensen (Trailhead Biosystems) [00:58:04]:
I mean, they can write. To me, that's that's probably the best. We also have a, you know, on the website for Trail Bio, www.trailbio.com. You can contact us. I'll be happy to to take your listeners' comments and see if I can get around. I can't promise to reply because the days are quite full, But, but yeah. Awesome.

 

Jeffrey Stern [00:58:33]:
Well, thank you again.

 

Jan Jensen (Trailhead Biosystems) [00:58:35]:
Thank you.

 

Jeffrey Stern [00:58:37]:
That's all for this week. Thank you for listening. We'd love to hear your thoughts on today's show, so if you have any feedback, please send over an email to jeffrey@layoftheland.fm m, or find us on Twitter at podlayoftheland or @sternjefe, j e f e. If you or someone you know would make a good guest for our show, please reach out as well and let us know. And if you enjoy the podcast, please subscribe and leave a review on iTunes or on your preferred podcast player. Your support goes a long way to help us spread the word and continue to bring the Cleveland founders and builders we love having on the show. We'll be back here next week at the same time to map more of the land.