BioTech Nation ... with Dr. Moira Gunn

In this week's episode of BioTech Nation, Dr. David Bearss, President and CEO of Halia Therapeutics, discusses inflammation and its reduction over a lifetime and in response to various incidents. He unveils the inflammasome, a recently discovered protein complex critical in regulating inflammatory responses and its potential in treating chronic diseases like myelodysplastic syndrome and Alzheimer's. Dr. Bearss shares insights into Halia's groundbreaking approach and his relentless pursuit of medical breakthroughs.

What is BioTech Nation ... with Dr. Moira Gunn?

Welcome to BIOTECH NATION !!! With understandable interviews requiring no background in science, BTN attracts a wide global audience. From everyday people looking for hope in treatments in development, to bioentrepreneurs interested in the experience of their fellow travelers, to venture capitalists looking for possibilities in cutting-edge breakthroughs, to scientists simply interested in the work of others, BioTech Nation is the voice of human endeavor, driving science to new realities for everyone. These interviews are drawn directly from the public radio program, "Tech Nation", which also can be heard in numerous global radio and podcasting venues.

Dr. Moira Gunn:

Today on Tech Nation, we're talking about inflammation, how it's there, and how we know it's being reduced both over a lifetime and in response to the accidents and incidents of living. Doctor David Bearss is the president and CEO of Halia Therapeutics. And now, doctor David Beers. Doctor Bearss, welcome to the program.

Dr. David Bearss:

Well, I'm excited to be here. Thank you.

Dr. Moira Gunn:

Now everyone is wary of inflammation, whether it's in their joints, in their gums, in wounds, anywhere in their body. And you talk about the inflammasome. That's like inflammation, but it ends with zone, s o m e. What is the inflammasome?

Dr. David Bearss:

Yeah. The the inflammasome is a a large protein complex that forms inside of specific types of cells in our body that regulates the immune inflammatory response. And it's something, you know, I'm a cell biologist. I have a PhD in cell biology and you know, I've taught cell biology at large, universities and I never have taught anybody about this because it's a fairly new discovery. We actually didn't know this thing existed inside of ourselves until just a few years ago, but it's, a we're starting to find out that this plays a major role in regulating not just not just the normal healthy inflammation, but the kind of inflammation that that is now associated with, a lot of of chronic diseases and we call it chronic inflammation.

Dr. Moira Gunn:

Now the inflammasome is part of, at least, what it's made up of are the red blood cells and the white blood cells that we have. Right? Those are all together?

Dr. David Bearss:

That's that's correct. Yeah. So the the immune cells are our white blood cells in our body, and so so when we produce immune, white blood cells, they they can react to different signals and can propagate a signaling to say to other cells, there's a problem here. It's time to come and fix this thing. And so that's part of our immune system is constantly looking for what we call danger or damage signals that that tell the immune system there's a problem and when they see that, certain immune cells will activate this complex of proteins that will then ask for more help to come to say more more of these immune cells need to come here and need to fix whatever whatever is wrong.

Dr. David Bearss:

So so there's a there's an interplay between all of our blood cells and how they how they get affected. So our blood cells are all produced in our bone marrow, and our bone marrow is inside it's a tissue that lives inside of our bones, and it's maybe the hardest working tissue in our body. It it it replenishes all of our blood, both our red blood cells and white blood cells, and even our platelets, which are are involved in clotting. It replenishes those every single day of our lives. So we're constantly turning over these cells.

Dr. David Bearss:

And so there's this this interplay, this connection in interaction between red blood cells, white blood cells, platelets, all communicating with each other. And it's remarkable that this this works really, really well for most of our life. But just like everything, it's impacted, by inflammation. It's impacted by as we age, it's impacted by our aging as well.

Dr. Moira Gunn:

Now tell me what happens as you age.

Dr. David Bearss:

Yeah. So, you know, I think all of us, especially, you know, as we get older, But when we but when we put a bunch of cells together in an organism, we we see that every organism that that lives on the earth will age. And our tissues you know, we used to think that aging was just our tissues got tired. They they they just ran out of juice to be able to do what they were supposed to do and they quit functioning properly. But aging is quite interesting and we've learned a lot about it and one of the areas that I've been focused on is what happens to your blood cells as you age.

Dr. David Bearss:

So as I mentioned, our bone marrow is a hardworking tissue. It's turning over red blood cells and white blood cells every day of our life and, you know, we used to think, oh, it just runs out of gas as we get older. It's not it's not as good as it used to be. But what we've discovered is as we accumulate damage over our lifetime, you know, we we these bodies of ours accumulate all kinds of of wear and tear. You know?

Dr. David Bearss:

We we can feel it as we age. Our our joints don't work as well as they used to. Our and our and our bone marrow has the same thing happening inside of it. So so there are these signals that I talked about, these these danger and damage signals that tell our immune system there's a problem here. And as we accumulate that damage over our lifetime, we start to see kind of this this low smoldering inflammation.

Dr. David Bearss:

So what we've discovered is that when you're young, your red blood cells and your white blood cells are produced by a lot of cells in your bone marrow. You have these cells called progenitor cells, or we call them stem cells sometimes, and those cells are producing all of your blood cells. And when you're young, there's lots of those kinds of progenitor stem cells making all of your blood. As you get older, you start to see that one clone, one single progenitor cell line inside your blood is producing most of your blood. And that that's remarkable when we first, as a scientific community, when we first discovered that a few years ago, it was just kind of an oddity.

Dr. David Bearss:

We said, oh, that's kinda weird. You know, why why does why does one cell take over as we get older? But what we've discovered now is it is a part of the aging process that seems to be predisposing us to a lot of other other conditions. So when we're young, our bone marrow's healthy. It's producing lots of blood cells from lots of different stem cells.

Dr. David Bearss:

As we get older, one particular clone seems to take over and produce most of our blood. And what we've discovered is that those clones are not normal. And as we age, we start to see accumulation of mutations. And when you have mutations in blood cells, they're not acting like a normal, healthy blood cell should act and so we're we're starting to ask the question, what does that mean? What does that mean to human diseases?

Dr. David Bearss:

Is there something significant about that? And I think we can say definitively there is something significant about it. It's having mutated blood cells is not a positive thing. And as we get older, we have more and more of them.

Dr. Moira Gunn:

Now at any age, if there's a problem with those cells that produce the the red and the white blood cells, you have a problem. You have a medical condition. What would be something we're familiar with?

Dr. David Bearss:

Yeah. So if you can't make blood cells, you know, I think the most familiar thing to everybody is the word anemia. And anemia just means you don't well, anemia means you're you you have a deficiency in red blood cells. So you're not able to either produce enough red blood cells or functionally, you're not able to to to make functional red blood cells. So that's, you know, in anemia, we we we all probably experience anemia at some point in time in our life.

Dr. David Bearss:

Women are more susceptible to it, than and children are actually quite susceptible to it. But but I think all of us are familiar with anemia. And anemia, there's there's a lot of causes. But as we've started to look at it, we've realized that that inflammation in our bone marrow is one of the main causes and drivers of anemia. So when you get inflammation, this inflammatory signaling in your bone marrow, it prevents the differentiation of these stem cells into red blood cells.

Dr. David Bearss:

And so we we can see a big percentage of the world's population. We're talking about billions of people, not not millions, but literally billions of people every year suffer from anemia, and a good portion of that is connected to inflammation.

Dr. Moira Gunn:

Now I have to say there's no doubt that you really want this to be working well.

Dr. David Bearss:

That's right.

Dr. Moira Gunn:

And all kinds of things could cause it to not be working well. And when it doesn't, you know, it's related to inflammation, and inflammation drives so many things. But let's look at what Halleah Therapeutics is focusing on. What are you focusing on in the inflammasome?

Dr. David Bearss:

So we discovered a few years ago that the inflammasome, this big protein complex in your cells, needs a lot of different components to come together at the right place and the right time to do what it's it does. And we we discovered that this gets messed up in different diseases, and that's where chronic inflammation that's that's where it starts. So we discovered a way to turn it off by blocking the assembly of this complex. And so we we have a little drug that we we we designed. We actually designed it on a computer.

Dr. David Bearss:

We we used what's called structure based drug design. So we we solved the structure of this protein that's part of the inflammasome, and we designed a drug to go in and bind to this this site on this protein that blocks its ability to to form this big complex. And when we do that, we can show that that we can dampen the signaling that comes from the inflammasome. And in fact, even cells that have had this this complex formed, we can watch that complex go away. And so, you know, it's a general mechanism that's associated with chronic inflammation.

Dr. David Bearss:

And so, you know, when we discovered this, we said, wow, you know, what can we do with this? Where is this important? You know, where should we try it? And, you know, because of my background and things that I've worked on in the past, I knew that there was this very specific bone marrow disease called myelodysplastic syndrome or MDS. So MDS is is a type of leukemia that's that's contained in your bone marrow.

Dr. David Bearss:

And, we know that it is completely dependent upon this pathway, the inflammasome, to to actually form MDS and to maintain MDS. And so it's a driver of this disease. So I called some of my friends that are experts in this area, some doctors that treat these patients, and I said, what if I had a way that I could turn this thing off? Do you think that we could look at that in human patients? And so we designed a clinical trial where we could take MDS patients.

Dr. David Bearss:

And right now, the way that we treat MDS, by the way, is these, these patients, they because they have such strong inflammation happening in their bone marrow, their bone marrow cannot make red blood cells, and they can't make good red white blood cells. And so what what happens is we call it a bone marrow failure. So the bone marrow just doesn't do what it's supposed to do. And the best way that we can treat it early on is we just give people transfusions. So they come in, they're very anemic, they feel terrible, and so we just give them blood.

Dr. David Bearss:

And and you can imagine that's that's not a great way to live your life, having to come in every week and get a transfusion. Some of these some of these people, that's what they have to do.

Dr. Moira Gunn:

So you're actually giving them red blood cells and white blood cells even though they didn't create them themselves.

Dr. David Bearss:

Exactly. So so we we just say, well, they can't make them, so let's just give them from somebody else. And so that's that's kind of how we're we're trying to treat the disease. It doesn't get at the core of the disease. Right?

Dr. David Bearss:

So that's not a really, an effective therapy because we're just trying to replace one of the problems. But but the real problem, the driver of this disease happens in their bone marrow, and it's driven by inflammation. So, obviously, we studied it in the lab and we said, well, what would happen if we treat it with our drug in a model of this? And what we saw was we could actually differentiate. So we could take marrow, bone marrow, and, you know, we just stick a needle into the into usually into the hip, the hip bone of of somebody, and we pull out some of their marrow, and we can grow them in the lab.

Dr. David Bearss:

And so patients that have MDS, we can show that they're not producing red blood cells and they're not producing white blood cells. And then we treat with our drug and and we start to see they're starting to differentiate, and we can see that they can move past that block that happened because of inflammation. So that got us very excited. And so, obviously, we had to jump through all of the the experiments that need to be done to get this ready to go into people. But we, we're actually treating real people with this disease now.

Dr. David Bearss:

We're asking the question, what does this do, to their their, ability to make red blood cells if we can turn off inflammation in their blood? And so we're we're excited about where we're at. We just launched this study a couple months ago. And so we hope by the end of this year, we can release some data and say this actually has an impact on on this disease. And by getting rid of inflammation, we can we can actually restore the body's ability to produce, red red blood cells and white blood cells normally again.

Dr. Moira Gunn:

So it's almost as if they still have the capability to produce the red and white blood cells. But the structure of the inflammasome, as it gets going, it stops it. It counteracts it.

Dr. David Bearss:

That's exactly right. So so it's it basically arrests these cells. So if you think about a stem cell, that's an undifferentiated cell. It just it can become all kinds of things that So there's a common progenitor cell in your bone marrow that can turn into white blood cells and red blood cells and platelets. And when you induce this inflammasome and cause this inflammation, it stops it from being able to do that.

Dr. David Bearss:

So if I can take that away, all of a sudden, we start to see the ability of these cells to differentiate into red blood cells and white blood cells and platelets.

Dr. Moira Gunn:

Couple interesting stories here. One is that so many of us have had surgeries. Small surgeries, large surgeries, and around the wound and in our bodies, there's inflammation. There's been an insult to your body. Is that the same kind of inflammation?

Dr. Moira Gunn:

Is that affected by this?

Dr. David Bearss:

Yeah. So it's interesting. The the inflammation that is triggered by a surgery, your body sees that as the same kind of damage response that it would if you, you know, broke your leg or you cut your finger. And so so, you know, obviously, we're going in and we're trying to excise out or trying to fix something that's wrong with a surgery, but we induce all this information. And we used to think, you know, back in the old days, 20, 30 years ago, the old days are scientifically Yeah.

Dr. David Bearss:

That that that that inflammation, that might be really good. Right? I mean, there because your body's responding to it and it's part of the healthy response to a injury or an infection. But what we've discovered is is that most of the inflammation after a procedure is actually not helping with the healing process. So so it actually, by turning on this inflammasome, which is exactly what you do when you have when you cause, damage, you're actually preventing the healing process.

Dr. David Bearss:

And that's why we try to, you know, put ice on on you know, when we have an injury is we try to stop the the immune response that's happening, and we take, you know, drugs like nonsteroidal anti inflammatories or other types of drugs that we've had available to us, but none of those drugs will turn off the inflammasome. And so so we're we're just trying to stop some of the downstream signaling that comes. But until now, we've never had something that could turn off the real driver of the inflammatory response. And so we're super excited about the idea. What happens if we just turn that thing off?

Dr. David Bearss:

What if we stop it? Could we heal faster? And what we've seen in the lab is it certainly looks like we can. So we can go in and do, you know, surgical procedures in the laboratory and show that we can see healing is actually faster when you turn off this this inflammasome signaling.

Dr. Moira Gunn:

Now we're gonna try that in humans?

Dr. David Bearss:

Absolutely. That was like, you

Dr. Moira Gunn:

should be silent anytime

Dr. David Bearss:

soon. That's right. So in fact, as we're we're recording this right now, we're we're actually treating people today. We just got the first go ahead to treat some people to see what happens post procedure. And the the the the nice thing about this is we can actually watch what happens in their blood.

Dr. David Bearss:

So after you have a a procedure, after you have a surgery done, you will see induction of inflammatory signaling in your blood. You can actually monitor that. So you'll see these signals go up and we can see what happens. So what we're doing is is we're seeing with with patients, what happens after their surgery when we don't give them their therapy to target the inflammasome and then what happens when we give them therapy to target the inflammasome and we see how different that inflammatory response is. And the nice thing from a drug development standpoint is that's a pretty short study.

Dr. David Bearss:

We we you know, we have a captured population of people that are having a procedure and then we we watch just over the course of a week what happens to their inflammation. And so it it can we can get a readout very, very quickly, which is exciting for us because sometimes we we design clinical studies that take literally years to figure out what's going on. In this case, we we we hope that we can see a signal very, very quickly.

Dr. Moira Gunn:

Now what are the first surgeries you're looking at?

Dr. David Bearss:

So we have a very interesting, situation that that exists where we are located. So we're our headquarters is is in in Utah, right south of Salt Lake City. And so the first surgeries that we're doing are actually connected to where we're at in Utah. So So we have a population of, young individuals that that are, headed out as missionaries for the, Church of Jesus Christ of Latter day Saints or the Mormon Church. And all of those missionaries that are going out, they all have to have dental exams and and they need to have their wisdom teeth removed.

Dr. Moira Gunn:

Whether there's a problem or not.

Dr. David Bearss:

Whether there's a problem or not.

Dr. Moira Gunn:

We we can't handle this if there's a problem when you're somewhere in the world.

Dr. David Bearss:

That's right. We send them all over the world. They go all over the place. And so it was just decided that prophylactically, it's a good idea to take your wisdom teeth out because for a young healthy person, it's one of the things that can actually cause a complication if they're in wherever, in Africa or, you know, where you know, wherever. We send them all over the place.

Dr. David Bearss:

So so, what we decided and we designed this study to to ask the question, well, when you when you pull your your 3rd molars or your wisdom teeth out, you actually cause not just the local inflammation in your jaw where you pull that tooth out, but it actually causes a systemic inflammatory response. You activate that inflammasome and your whole body says, hey. We've got a problem here. So we're we're actually doing in in literally today, we're we're we're dosing patients where we can see what happens if we extract this tooth and we and we turn off the inflammasome. What happens to the the signaling for inflammation?

Dr. David Bearss:

And the implications here are big. So if we can show that we can block by blocking the inflammasome, we can block that systemic inflammatory response. We hope that leads to faster recovery after a surgery by suppressing inflammation. So we can we we already know that that if you can get back to work and get back to, you know, activity quickly after surgery, your your outcomes do are better. If you feel lousy and you're just laying around for a while, you actually do worse.

Dr. David Bearss:

And so trying to get people back and and recover quickly is is a really important important part of the recovery from, surgeries. And inflammation plays a big role in people not feeling like they they can get back and and get back to normal activity. So so if it works there, the next step is, let's see where else it works. Does it work in in, you know, in in some of the standard places that we look is bunion surgery, tummy tuck surgery. Those are those are also very very captured populations, but but even, you know, in knee replacements and hip replacements and very common surgeries that we have all the time.

Dr. David Bearss:

We know that this pathway is activated, and we're very, very interested to see if we can we can help people recover faster by turning off that information.

Dr. Moira Gunn:

Well, I mispronounced the name of your company when we first met. I said Halia, h a l I a. And I was like, no. It's it's Halia, which is which is Hawaiian. You guys are all over the place.

Dr. Moira Gunn:

Okay. How do you how did we get this name halia?

Dr. David Bearss:

Yeah. Yeah. You know, I, it's, myself and, one of our cofounders, a Hawaiian scientist, and there's not many scientists from Hawaii. So he's kind of a he's he's kind of a unique individual, but, his name is Keoni Kawe. And so Keoni and I, got together to start CALIA with the idea that that we could target inflammation in the brain.

Dr. David Bearss:

And we actually, discovered this in a very interesting way. So, Keone is a human geneticist. So he studies risk factors based off of our genetics. So he looks at variations in in genes and and what that does to risk for different diseases. So he's looking for, you know, the the places in our DNA where we have differences and how that that that is correlated with our risk for developing different diseases.

Dr. David Bearss:

And his specific interest has been in neurodegenerative diseases like Alzheimer's. And so he came to me and said, hey, I discovered something really interesting. So there's there's a a very well known risk factor for Alzheimer's disease. It's called the APOE4, and it's a it's a polymorphism and you I guess you call it a mutation, but it's a it's a it's a different DNA sequence in this gene called APOE. And if you have this this flavor of that that, that gene, your risk for Alzheimer's is quite high, relative to the rest of the population.

Dr. David Bearss:

So he was studying this, and he actually found a family. And once again, it comes back to Utah. We we we have large families in Utah usually. And he found a family in Utah that had this polymorphism, the APOE 4. But no nobody in their history, their medical history, and their family, nobody got Alzheimer's disease.

Dr. David Bearss:

So he actually organized a family reunion, got all those people to come, and and, they they all consented to be studied to see why with this this genetics that should should predispose them to Alzheimer's, why none of them got Alzheimer's. And so we were able to sequence all we sequence over 200 individuals in this family. And we discovered they had another unique DNA, very or polymorphism or mutation that actually looked like it was associated with preventing Alzheimer's. And so when we started the company, the whole goal of the company was to figure out, well, what does this do? And we started the the the name of the company, Halea, is a Hawaiian name that means fond memories.

Dr. David Bearss:

And so we started with the idea that that, we could we could target Alzheimer's. And in fact, we haven't given up on that. In fact, very, very soon, we should be, announcing that with our second drug that we're moving into the clinic is, is actually targeting this exact pathway that we discovered and trying to replicate what we discovered genetically in this family with a new drug that can have the same kind of activity. And in fact, it right comes right back down to inflammation as well. So what we discovered is this family has a mutation.

Dr. David Bearss:

We call it a resilience mutation because they're resilient to a lot of things. They they have less heart disease. They have less cancer. They have less Alzheimer's. And it's interesting that it's due to their ability to have lower response to inflammation.

Dr. David Bearss:

So we're excited about, the idea that we can take a genetic discovery and translate that into something that we could actually use as a therapeutic.

Dr. Moira Gunn:

You know, here we have Dave Beers, you know, drug hunter. Drug discoverer, doctor Beers. Very impressive. And I do have a question for you, along these lines. I mean, you have founded 8 biotech companies.

Dr. Moira Gunn:

You've discovered many drugs. 16 of those drugs have actually moved into human clinical trials. Then I have to tell you, that's an impressive record. How is your current experience with Halea the same, and how is it different from your earlier experience?

Dr. David Bearss:

Yeah. It's, you know, it's been it's it's been an amazing career for me. I I I love what I do. I get up every morning thinking today could be the day we make a discovery that changes the world and and, you know, that's that's not hyperbole. That's real.

Dr. David Bearss:

Right? I mean, we can actually find things that that change, diseases in people, and that's just amazing to me. So so when I first started, I was very naive in terms of of starting a company. And and and really my motivation to start a company is I discovered I was a professor. I was, you know, in in the lab, you know, doing research there, and and we discovered something that we thought could be a new therapy that could could help people.

Dr. David Bearss:

And I went to a mentor of mine that that, I learned a lot from and and said to him, well, how do I how do I take this from my lab and turn it into something that could help people? And he said, well, you're probably the only person in the world that's gonna believe in this. And so if if you wanna see it move forward, you probably need to do it yourself. And so I actually took the leap and and just said, okay. I walked away from a tenure track faculty position at a major research university and just decided I'm gonna start a little company.

Dr. David Bearss:

And I barely even knew what a a a stock was, a share in a company. I hardly knew any of that. But thankfully, I I had a great partner that that, helped me, put together the first company. But, you know, I had no idea how hard it was to raise the money and to to go through all the process of of, getting the, supporting information to show that the the drug could could actually be safe and potentially effective in people. And so I guess what's different about Halia is that I had 7 other tries to learn a lot of stuff that that, and make every mistake that you can make.

Dr. David Bearss:

And, hopefully, I'm not making very many anymore. But, I tell people all the time, I, you know, I I earned all the white hair that I have because I, I've I've probably made every mistake that you can. But but what's kept me going is, you know, I I really wanna make a difference in people's lives. I I lost my grandfather the year I was born. Never had a relationship with him.

Dr. David Bearss:

Didn't don't know him. I have one picture of me as a baby with him holding me, and that's it. That's all I know about him. And I lost my mom when when, when still when she was young, both of cancer. And, I just decided, you know what?

Dr. David Bearss:

If I can spend my life and make it so other people's moms and grandpas can be around a little longer, that's not a bad life to live. And so so for me, that's what keeps me going every day is is can I make a discovery that can keep people's grandmas and grandpas and moms and dads around a little longer? And and, you know, it's it's it's it's amazing to me that that, you know, we've been able to to to work on projects that that, you know, are now approved drugs, things that that people use, and they have extended the life of people. But it's, it's never enough for me. I'd I I wanna have number 17, 18, 19, 20, you know, to keep finding finding the next one.

Dr. David Bearss:

So, I I'm not gonna stop.

Dr. Moira Gunn:

Doctor Behar, I'm thrilled that you're not gonna stop, personally.

Dr. David Bearss:

Thank you.

Dr. Moira Gunn:

I wanna thank you so much for coming on. I hope you come back, visit us again.

Dr. David Bearss:

I I'd love to. I'd love to tell you the the you know, when we get some results, show you what's happened and and what the next big thing is.

Dr. Moira Gunn:

You're on. You're on. Thanks again.

Dr. David Bearss:

Thanks a lot.

Dr. Moira Gunn:

Doctor David Bearss is the cofounder, president, and CEO of Halia Therapeutics. More information is available at haliatx dotcom. That's haliatx.com.