Cell Therapy The Power of Pluripotent Stem Cells

2020 is the decade of the cell. The next 10 to 20 years are going to be huge for developing cell-based treatments and no one is a better guide into the world of this research than Brian Culley, the CEO of Lineage Cell Therapeutics, a company making enormous strides using pluripotent stem cells

Check out Lineage Cell Therapeutics on YouTube.

Bryan Culley’s backstory (3:00)

  • Culley has always been enthusiastic about science.
  • Path of basic to applied research to business management side of research.
  • Culley likes that, as CEO, you get to see all the parts of the business puzzle and understand what path to take their company on.
  • He is very involved in the novel science his company is developing.

Lineage Cell Therapeutics’ work (7:40)

  • Using Pluripotent stem cells, aka cells that can become many different types of specialized cells in the body, to become special cells that help repair various parts of the body.
    • Pluripotent stem cells can divide forever
    • Cells can be replicated forever.
  • Specialize in spinal injuries, dry age macular degeneration, and oncology, or cancer treatments
  • Lineage uses a process called directed differentiation to create specialized cells.

What is the “recipe” for developing differentiated cells? (13:00)

  • Developing the right formula is a major challenge of this work.
  • It’s a process of trial and error, but also one that is occurring time and time again in every multicellular organism.
  • Process controlled by molecules
  • Lineage tries to create that process in a test tube.

Spinal Cord injuries

  • After a spinal cord injury, spinal cells die and result in paralysis.
  • Culley’s company injects new spinal cells into the spinal column that help the spinal column heal and start sending signals again.
  • Not complete repair, but results in increased mobility for injury victims

Macular Degeneration or blindness (22:00)

  • In macular degeneration, or blindness, retinal cells die off
  • Lineage treatments replace the dying cells with new, healthy retinal cells.
  • “Retinal restoration”

Oncology (24:30)

  • Tumors are aberrations of the body
  • They’re your own body going haywire.
  • In order to help the body discern between healthy cells and cancerous, tumor cells, Lineage manufactures dendritic cells that help other cells identify tumors and cancerous cells.

How big are the markets for these types of treatments? (27:45)

  • The markets currently are billions of dollars for small markets
  • There aren’t FDA approved treatments right now because we don’t know what’s broken. Approaching from a cell transplant angle may be a multi-billion-dollar market.

What moves the needle in terms of investments (31:20)?

  • Everyone wants to know, when will I make a lot of money from my investment?
  • You never know when the stocks will take off.

How will investors know when Lineage is taking off? (35:00)

  • Watch for the data updates
  • Watch for partnerships developing as well.
  • Stay up to date with the website.

Fun Questions (38:00):

  • What could be possible with Lineage Therapeutics?
    • Culley wants Lineage to be associated with major strides in the field
    • Restoring retinal tissue.
      • Identify patients early and stop progression of disease.
      • Prevent vision loss.
    • Treating spinal cord injuries and improving patient locomotion.
    • Dendritic cells will be an important cell treatment in oncology.
  • What is Culley most excited about in the biotech world?
    • COVID vaccine development

Like what you hear? Click subscribe in Apple Podcasts, Spotify, Stitcher, or wherever you get your podcasts. Keep up with latest news, episodes, and Biotech updates on Instagram @SimpleBioTech. If you want to know which BioTech companies host James Ruhle is currently excited about, connect with him on Angel List, Angel.co/jamesruhle

For the full transcript of The Simple BioTech podcast Episode 9 Click Here

James (00:01): Through my research and conversations with people a million times smarter than me, I’ve come to the conclusion that 2020 is the decade of the cell when it comes to understanding the cell and the insane rejuvenative benefits that are going to come with that. We’re right at the tip of the iceberg. The next 10 to 20 years are going to be a wild ride when it comes to cell therapy. And there’s few people on this planet better to help explain that than my guest today. Ryan coli, Brian is the CEO of lineage cell therapeutics, a publicly traded company on the New York stock exchange. And they’re making some groundbreaking progress using the power of plurry potent STEM cells. One thing I love about this interview is just how obviously passionate Ryan is about the work that he’s doing. It’s not often that you see CEOs that are this deep in the weeds of every facet of their company.

James (01:00): So without further ado, I present to you today, mr. Brian Cooley, the human experience is changing and it’s going to happen a lot faster than you think the world is going to be a vastly different place in the next 10 to 20 years because of what’s happening in the biotech industry right now, welcome to the simple biotech podcast. My name is James rule, and I’m your host. The goal of the simple biotech podcast is to interview the researchers, founders, and investors that are working directly in the industry and to translate what they’re working on into simple and easy to understand language. If that sounds like something you’re interested in, let’s get started.

James (01:47): Hi, Brian, thanks so much for joining me today and it’s my pleasure, James. Thank you. You know, I’ve had an awesome time over the past few days, doing my research, looking into lineage cell therapeutics, I actually came across your guys’ YouTube channel and I was blown away by some of the patient highlights that you guys show on the YouTube channel. And for anyone listening, I highly recommend head to YouTube type in lineage, cell therapeutics. It’s really amazing, awesome stuff. We’re going to talk about this more in the interview, but basically what they’ve done is they have people who have are paraplegic have been in some sort of serious accident who before their treatment with lineage were unable to move completely unable to move. And after their treatment, these patients are now able to text hop on social media, play video games, drive just seeing how happy those patients are to do things that you know, me and you and everyone listening to this takes for granted every single day. I got to say it was pretty touching. You guys are working on some pretty ridiculously life changing science. So before we get too much into that, I like to start every interview with, uh, just a quick backstory on you. Brian, you’ve got quite an impressive history in the biotech world. You’ve worked in leadership positions at multiple publicly traded companies. So I’m curious, how did you get into all this? What was the spark originally that ignited defier your passion for you to get involved in this groundbreaking industry?

Brian (03:16): Thanks, James. I think it is that it’s a fire. It’s a passion. The specific path is always interesting and unique and never straight, but the underlying enthusiasm for science as a discipline is something that’s been with me ever since I was a little kid. I even remember when I was very young, putting a bunch of ice cubes and water in one glass and just water in the other and filling them up to the very top and wondering if the ice would melt fast enough that the water would spill over one cup compared to the evaporation. And I was very young and I was doing experiments like that. So I’ve always been interested in science and the way that the world works. And I just sort of, you know, somewhat randomly and it’ll follow the path that began with basic research, working in a laboratory and then went into applied research, which is more industry like figuring out how to use the rules of science. And then I went into the business side of it, licensing technologies, basically buying and selling technologies and eventually found myself running three public companies. But I always still rely on that scientific background as the main driver and trying to make the world a better place. Yeah. And you know, I’ve always wondered, I’ve talked to a few,

James (04:29): Those of these publicly traded companies. Now, these biotech publicly traded companies. And as a expert, you know, as someone who’s got obvious biotech chops, you’ve also got to have some serious business chops as well. What exactly is the role of a CEO in companies like this? I mean, maybe you can share a little bit about that.

Brian(04:49): I think of it as direction. So the nice thing about being CEO and to be fair, there are some bad things, but the nice thing about being CEO is that you have responsibility for every area of the business. So you have a luxury of sorts of being able to see how all the moving pieces fit together. Now, the person who’s in charge of manufacturing or regulatory, they know their area best, but they might not spend have time or background to spend thinking about how the financial part or the investor part or the clinical part in some ways even fits into what they’re doing. So being CEO, you’re able to see every single piece of the puzzle and you can try to navigate the best path forward. It’s not always a forward path. There are setbacks. You have to assess risks with imperfect information about those risks and so forth. But I think that having a, both a scientific and a business background does help a lot of CEOs be able to understand all the different areas of their business and try to make good decisions. And then of course, you’ve got the personal side, you know, how you interact with people both inside and outside of your company and all of that stuff has to come together. And hopefully, you know, if you make a couple of good decisions along the way, you’ll create value and ultimately create new therapeutics.

James (06:08): Yeah. It must be a really exciting industry. And how much of the science are you involved with these days?

Brian (06:12): I’d say a lot. And partly because we really operate in a new area of science. It’s been around for a couple of decades, but it’s also very young because it changes so quickly. So I definitely do not sit back and wait for the reports to get onto my desk and read the summary and move on. I’m intimately involved in how we run the business. And I hope my team doesn’t mind that I think I add value, but I’m absolutely very closely involved in the science. Not just because I’m interested in it because sometimes I’m able to identify or appreciate certain risks or opportunities that others don’t for the same reason that they only see one piece of it. So I try not to get in the way, but I definitely need to be close to the action.

James (06:57): It’s really great to hear actually hearing that a CEO is still so in the weeds of the real, uh, the gold that’s being mined at their company, you know, and I think a lot of investors or potential investors that would hear about this would like to hear that as well. You hear a lot about CEOs that really have no idea what’s going on in the trenches. And I think that’s really cool that you’re still so heavily involved in that area of the business. Yeah. I certainly like it too. So let’s actually talk a little bit about your company and your business while you guys are working on, I’ll try and explain with my childlike understanding of what you guys are doing, and then you correct me with anything that I get wrong. All right. Sounds good. Okay. So lineage cell therapeutics, you guys are using pluripotent STEM cells.

James (07:38): And for those that don’t know, pluripotent STEM cells are basically cells that can turn into anything. They’re the first version of a cell for lack of a better word. And you guys are taking those pluripotent STEM cells and you’re working on three different areas of human issues. One of them being spinal cord injuries, one of them being dry age related, macular degeneration, and one of them being oncology and cancer. So you guys are essentially taking these pluripotent STEM cells and you’re coaxing them somehow. And I do want to get into that a little bit, how exactly you’re doing this, but you’re somehow telling these pluripotent STEM cells, which cell they need to turn into, and then you’re injecting those cells in one way or another into the patients, whether it’s a cell that helps with spinal cord injuries, whether it’s a cell that helps with dry age related macular degeneration, or whether it’s a cell it’s going to help with oncology with boosting the immune system for fighting off cancer cells. That’s what you guys are essentially doing, correct me if I’m wrong,

Brian (08:36): You’re off to a great start. I would not be unhappy if someone was describing our company to somebody else and they use those words, I would be pretty satisfied because it can get very technical and it can get difficult, but you’re absolutely right. The fundamental premise here is that plural potent STEM cells do have the ability to become any cell in the body. Pluripotent STEM cell is it has not written its own history yet. It is still able to become a kidney cell or a brain cell or a bone cell or a blood cell. It can become any of the 200 types. And what’s also really interesting about pluripotent STEM cells is that they can divide forever without losing their genetic information. And so what I mean by that is a normal cell in the body be able to replicate say 30 or 42. Hi, but every time it replicates, there’s a little bit of damage or error that occurs to the DNA.

Brian (09:37): And so those cells cannot be replicated forever, but the cells that we work with can be replicated forever. So you could start with a single cell and you could multiply it. It’ll divide into two and then divide into four and divide into eight, 1632. And it never changes. It’s truly clonal. Okay. If you divide it 30 times, you’re well over a million, you can get to Billy and you could even get to a trillion cells, all which tags exactly match that first cell. So the reason why I mentioned this is that that allows you to create an enormous scale. We have frozen cells, which can be thawed. They can be divided, you know, you just feed them and they start growing and dividing and then you can just harvest them and freeze them back down. So on one hand, we have an unlimited supply of these cells.

Brian (10:21): The next part is, well, how do you coax them to become a specific kind of cell? It’s sort of like a, a, it’s a blank cassette. And you want just to put journey ACDC and led Zepplin on there, right? Strange combination. But you know, there are strange cells in your body. So what we do is we expose the cells to different chemicals and different conditions for different amounts of time. And that process is called directed differentiation. So we don’t let them divide and become whatever they want. We say, Hey, everybody, you all have to become a retina cell. So here’s the right kind of foods give you to make you become a retina cell. Here’s the right information that we don’t manipulate the DNA. We don’t go messing around with the DNA because that can get a little dangerous. So we just coax them and bring them to a point where we end up with, in our case, we can manufacture in a three liter bioreactor.

Brian (11:18): So like a large jug of milk. We can manufacture 5 billion retina cells, which are 99 and a half percent pure other things that are in there minimal. So we have the ability to essentially make pure populations of discrete kinds of cells. And then we transplant those cells into the body. So if you have retina cells that are dying off and you need new retina cells, that’s what we make. If you have an injury from your spinal cord and you need spinal cord cells, that’s what we make. Or if your immune system is not working to its full potential. I was just reading yesterday about how COVID-19 wipes out the dendritic cells. Those are the cells that we make. So we are really not using STEM cells as anything other than starting material. We don’t put STEM cells into people. STEM cells are just our source of material. And then we make them into fully mature, differentiated cell types. And then we just do straightforward transplant medicine. So it’s really more like a transplant of tissues and cells than it is any of the magic of STEM cells themselves.

James (12:27): I think that’s a pretty big differentiation there between what people may think traditionally, when they hear STEM cells, you know, they may have heard about people going down to Panama and injecting STEM cells, you know, illegally in their arms. And this is obviously something completely different. So this is essentially taking those, that first version of the STEM of the cell that can turn into any type of cell. You figured out a recipe for the spinal cord cells for these immunotherapy cells, there’s oncology, cancer fighting cells. How do you figure out that recipe to make the pluripotent STEM cell turn into this

Brian (13:01): With great difficulty? So it took many years, I’ll give the example of the retina program. So there’s a gentleman by the name of Benjamin Rubinoff, who spent many years trying to figure out how to take one of these blank slate cells and turn it into, or convert, converted into a retina cell. And eventually he was able to figure it out. Now it wasn’t the most efficient and it wasn’t perfect and there were issues with it, but he could imagine that if you could improve upon that process, that someday you could be manufacturing retina cells outside the body, implanting them into the eye and saving vision or improving vision. And so he spent many years in an academic environment trying to figure that out and then spun out a company to begin working on that. And then we eventually acquired that company. So I think there’s a lot of trial and error that goes along with it.

Brian (13:57): But if you think about in the body, if you think about from the process of development, right, a single cell eventually has to become the creature, whether it’s a mosquito or a mammoth, it has to become it. So how does that cell both divide and differentiate to become the thing that it’s going to be? And the answer to that is there are molecules, which that cell are exposed to, which help it understand what’s top. And what’s bottom from a developmental perspective. And so one side of the cell gets a little bit more of a certain molecule and that molecule says, Oh, I want you to be more neural. And the other side of the cell is getting a different concentration of a different molecule that says, no, we’re kind of more limbs and bones and circulatory system. And when that cell divides, now you have separation, right?

Brian (14:49): The cell up above got this message to be kind of more neural. And the cell down below got this message to be more own, like it also continues to get that message and amplifies it. So as you continue to grow as an organism, there are more and more messages and more and more amplification to say, okay, this little patch of cells, they’re all going to become the spinal cord and the brain, these cells over here, they’re going to become the limbs, lower limbs of the frog or the person or whatever. And all of that is run chemically. It’s all just time and exposure to different chemicals. So we basically pull that into a test tube environment where we can give the right kind of messages and the counter messages. Sometimes you get messages that say, don’t be this. I don’t want you to go sideways. Don’t be a kidney. Everybody stay together here. And by doing so and figuring out the right amount of exposure and the right compounds, you can essentially create just a pure population of a single type of cell.

James (15:45): It’s sounds like it’s not easy to figure that out.

Brian (15:48): It’s not easy. And from an FDA perspective, one of the things that the FDA cares tremendously about is consistency. So you can’t go to the FDA and say, well, here’s a batch of 99% pure retina cells. And then here’s this other batch. It didn’t go as well. They’re only 80% pure. And we don’t really know what the other 20% is, right. That doesn’t work. So one of the challenges in cell therapy as a whole is purity. You’ve got to have consistent manufacturer of the thing that you’re trying to make. And if you can get purity and you can get scale, or you can get reproducibility and you can get scale, then you’re well on your way toward approvable products. Right?

James (16:28): Right. So this isn’t something where you can just be like, all right, well, we got that figured out. So let’s now figure out a knee, knee, joint, knee joint cells. Yeah. Send those, those, this is a really long, complicated process just to even be able to figure out how to turn the pluripotent STEM cells into

Brian (16:44): Whatever cell you’re trying to turn it into. That is correct.

James (16:48): So let’s talk about your, the three, the three assets you guys have, you have OPC one, which is the spinal cord injury. And that one is, is in phase one slash two a yes, you have oxygen, which is the dry age related macular degeneration, which is for people that aren’t familiar with, that that’s people that have lost their eyesight due to age. And that’s also in phase one slash two eight. And then you have the oncology. And is that for the oncology one, which is back to, is that just general cancer or is it focused on any one person

Brian (17:18): Take your type of cancer right now it’s in a form of lung cancer, but it’s applicable to both solid tumors, as well as liquid tumors, like tumors of your circulatory system, your blood system.

James (17:30): One is in phase one. So could you explain a little bit about what the difference between phase one, phase one and phase two phase three? What the difference between those?

Brian (17:39): Yeah. This is a real challenge in the industry because it seems like it should be very cut and dried, but it’s not, there’s a lot of flexibility in what you call trial, but generally speaking phase one studies are the first time you put a intervention or a therapeutic into a human. And you’re really just looking to see how it’s tolerated. You’re asking questions around safety. A phase one, two way can be a number of different things. So for example, if you ran a phase one trial in a small number of patients, let’s say 10 people and you thought, Oh, that was pretty cool. They tolerated it. Well, you might then move into doing an extension of that study, or you might move into patients that have a different form of the disease. You might still be asking safety questions, but if you’re starting to look at efficacy, then you tend to see studies that are called a one two way or just two way. So for our programs, even though these trials that we have initiated are looking at safety first and foremost safety, we also can’t avoid, uh, getting some information about efficacy. So we have called these phase one, two ways because they do provide some information about ethicacy. And as you’ve noticed, some of that efficacy seems really exciting.

James (19:03): Some of this stuff is really exciting. And I do want to actually go into some of the, some of the results that you guys have. As I mentioned at the beginning of the podcast, a little bit already about the spinal cord injury, which is really, really awesome stuff. But can you tell us a little bit about the results you guys have seen with the dry age macular? Sorry, it’s quite a tongue full age related macular degeneration and the oncology.

Brian (19:25): Well, let’s start with spinal cord injury because it really is notable and exciting. So typically what happens is, is you get a young man, this is the most common thing a young man he’s surfing or driving, or, you know, falls off a diving board the wrong way. And he, he suffered an injury to his spinal cord and that it’s not a complete severing of the spinal cord. It’s an injury, it’s a wound. And the area around that wound of course, is going to experience inflammation and inflammation can lead to cell death. So if you imagine the spinal cord as being along electrical cable, cause that’s basically what it is, you’re nicking it, you’re cutting it. And if it’s cut badly enough, you can lose the ability to carry information up and down the spinal cord. And so that’s paralysis. So we’ve had people who have very high levels of cervical paralysis.

Brian (20:18): So very high in the neck and they have lost movement, not only in their legs, but also in their arms. So these are individuals who essentially have no movement, they’re on a respirator to help them breathe. And they have no feeling in their limbs after the immediate injury, about three weeks after the immediate injury, the inflammation starts to go down and that’s where we come in and we administer brand new spinal cord cells. There’s a special category. I won’t get into the details of the technical version, but let’s just say the patient has had a bunch of spinal cord cells die. And we come in and we inject new ones. So where we come in and we fill that space, cause there’s literally a cavity. That’s the term or a hole where there’s no cells. We inject ourselves millions and millions of our cells into that space.

Brian (21:08): And those cells have the ability to manufacture the insulation that helps carry messages up and down that wire. And what we are trying to demonstrate is that after an injury that we can come in three to six weeks later, we can inject ourselves. And remember they’re not STEM cells, they’re not blank slate cells that are waiting for a signal to know what to do. These are already developed spinal cord cells that have the ability to make the insulation of your spinal cord. And so we inject those. And what we’re trying to do is provide more recovery, more motion to these individuals. So it’s to help their healing. And the reason why that’s so profound is it, if you can help someone regain a little bit more mobility after their injury, specially if it’s mobility in their arms and legs, you provide for them an astounding new level of freedom and quality of life.

Brian (22:02): Because the difference between being able to type or not type is life changing, it sounds straightforward, but it’s really life changing. And we have a young man who couldn’t move his fingers in his wrist and he can now type 30 to 40 words per minute. So those kinds of incredibly powerful, additional recovery attributes that we are providing to individuals, that’s what we are working on now. And that’s what we’re so excited about. And you can do this in addition to all the other physical therapy and all the other treatments that people want. There’s no reason you couldn’t include that on top of what we are doing. So that is a, as I say, very powerful and very motivational for us in spinal cord injury in macular degeneration or, or what I’m going to just call blindness going forward. It’s not every kind of blindness, but it’s an enormous kind of blindness about almost 2 million people in the U S suffer from this particular kind of blindness called dry macular degeneration.

Brian (22:59): What happens is that retina cells die off. So it’s not the spinal cord cells. Of course, it’s the retina cells and nobody knows why they die off. So for the companies like the Pfizers and the Bristols of the world, if you don’t know what’s broken, if you don’t know why these retina cells are dying, it’s really difficult to make a therapeutic, to treat them. And so we have no therapies for this kind of blindness today. Our solution is different. We don’t care that we don’t know why the cells die off. We don’t need to understand why the cells die off because we’re replacing the entire cell. So as I described earlier, we can manufacture billions of these retina cells. And then we can transplant them into the eye where your old retina cells have died off. And if they get in there and they integrate in there, they’re happy and they settled down and they start doing retina things.

Brian (23:50): We think that that’s going to be really important to slowing that disease. It’s a progressive disease. If we can slow that disease, or more recently, we even announced that we were able to reverse it and no company has ever done that before. And that’s called retinal restoration. And that is something that we think is reflective of the power of cell therapy. I mean, this is what people 15 years ago were saying cell therapy was going to do. You’re going to be able to, you know, manufacture organs and replace body parts. It’s literally happening. Now. We’re manufacturing outside of the body retina cells. We’re injecting them into the eye of humans, not of rats and mice, right of humans. And we are seeing improvements in vision. And we are seeing, I’m going to call it colloquially healing of these lesions or these wounds in the back of the eye.

Brian (24:39): And we think that that is incredibly exciting. And then thirdly, we have the oncology program. One of the interesting things about oncology is that you can treat a tumor as an invader. It really is an aberration or it’s your own body going haywire. And it’s always very difficult. And this is the underlying principle of cancer treatment. It’s always difficult to give a treatment that kills tumor cells, but doesn’t kill normal cells. And that’s why, you know, everybody understands about hair falling out and problems with chemotherapy is that the medicines that we have, don’t do a great job of telling the difference between a tumor cell and a normal cell. And that information discerning between tumor cells and normal cells. That information is carried by a kind of cell called a dendritic cell. And so that’s what we manufacture. We manufacture dendritic cells and we inject them into patients by the tens of millions.

Brian (25:32): And those dendritic cells are loaded with information about it’s a marker of what a tumor cell looks like. And so they flow around your body, waving this flag saying, Hey, I know what a tumor cell looks like. And then your immune system sees that information from the dendritic cell and says, Oh, okay, that’s a tumor cell. I’m the guy who goes and kills those things. So thank you for the information dendritic cell. I appreciate it. Lineage for you giving me this information. I’m going to go kill the tumor cell. So again, it’s a third and very different approach where each case we manufactured the specific cells that are required to perform a specific job that your body is losing or lost the ability to do. And by transplanting those cells into the body and replacing that function, replacing that activity, we think we can get clinical outcomes to help people.

James (26:21): Wow. Well, first of all, congratulations that to be a part of a company that’s doing all this stuff and it must be really, really exciting for you. It is. It’s very fulfilling. Yes. I mean, just being able to see all these results. Yeah. Congratulations. So to just go over it again really quick, from my perspective, essentially, you’ve got the spinal cord injuries, which when someone injures their, uh, spinal cord, they lose a large amount of those cells. What you guys are doing. You’ve created those cells in a lab and you re-inject them back in, and you’re seeing fantastic results. People who could not think about potentially typing or waving or driving are now able to type 40 words per minute. That’s really, really amazing from the dry age related macular degeneration. You guys are essentially just as we age, we lose these cells die off in our eyes and you guys are just adding those cells back in.

James (27:11): We don’t know why they die off, but you guys are adding it back in and that’s fixing the problem more or less. And then for the cancer, basically with cancer, it almost seems like it’s a, an enemy that’s coming into your body and you guys are creating cells, dendritic cells that kind of raise the red flag. And they’re like, Oh no, we see you cancer cells. And they fight them off. That’s really exciting for all of that. It’s got to be not, I mean, not only fulfilling for you to be running a company like this, but it’s got to be exciting for the growth of the company. That, I mean the potential market that you’re going to be tackling, which brings me to the next part of the conversation I’d like to get into just a few business questions about lineage. Of course, how big are the markets for these assets? I mean, you talked about blindness, you talk about cancer, talk about spinal cord injuries. I mean, these are some, what I would assume are some massive industries, massive markets. And how big of a chunk do you think that lineage can attain of that?

Brian (28:04): One of the most compelling things about working in our field is that we’re a leader, we’re a pioneer. And so the competition is actually quite sparse. And when you don’t have as much competition, you can get really excited about potential revenues. So let me give you an example about dry macular degeneration. There’s another form of macular degeneration called wet. So there’s dry and there’s wet. Now people have been able to figure out treatments for wet AMD and those treatments are selling more than $10 billion a year to address wet AMD. And as I’ve mentioned earlier, there are no treatments yet for dry AMD. But the amazing thing is they’re about eight times more people with dry AMD. So you have a market in ophthalmology today, which is selling $10 billion, mostly from just two therapies. And it’s the little one it’s the baby market, right? It’s the one that not as many people have is this wet AMD we’re working in dry MD.

Brian (29:05): And again, it’s sort of confounding, but the answer is that you don’t have FDA approved agents in dry AMD because nobody really understands what’s broken. So coming in and approaching it from a transplant perspective rather than a, a molecular pathway perspective, I think gives us an opportunity for a multibillion dollar program and the same with oncology. I mean, there’s nothing about lung cancer that is connected to what we’re doing. We could go into ovarian cancer or breast cancer or adrenal corticoid cancer. We can, we can go into leukemias and things. So the opportunity there, it vastly exceeds our capabilities. I mean, we don’t have enough resources to go after every cancer type, but if we can get a win or two, that will help us be able to attract the capital to go into many more areas. And in spinal cord injury, there aren’t as many individuals who suffer from spinal cord injuries, but again, they have very few options and the cost of healthcare and helping an individual who is a quadriplegic can run into the low single millions of dollars, upwards of $5 million.

Brian (30:21): So if you were able to change someone’s care from 18 to 24 hours, right, nearly around the clock care, if you can give them some mobility in their arms so that they can feed themselves so that they can change their clothes, that they can bathe themselves so that they can communicate online. You have changed their care down to maybe four, six hours a day and the savings over lifetime, especially because these tend to be young people with a lot of lifetime ahead of them. There’s a very compelling economic argument to be made. So all three of our programs have enormous commercial opportunities associated with them.

James (30:57): That’s a fantastic answer. And I think for this next question, you may be the perfect person to ask because you’ve been involved in so many publicly traded biotech companies when it comes to investing in these companies, what does typically move the needle? Because you guys are still in phase one and really for these to be mass produced, to be unleashed to the public, I believe you have to finish phase three, correct?

Brian (31:21): You can be public at sort of any time. You don’t even have to be in the clinic to be public, but everybody always wants to know, when am I going to make a lot of money from my investment, right? When, cause what happens is that people get introduced to our story or stories like it. And they say, wow, this company is awesome. I want to own this stock. And then they wonder why the next day it hasn’t tripled. Like why doesn’t everybody else see it? And the answer is you just never know when these stocks are going to take off. And I have a very specific example and that’s Tesla. I was interested in that company when it was a $30 stock and very quickly it went from $30 to $200. It was the exact same company. I have no idea. I mean, I was watching all their news.

Brian (32:06): I was really interested in this new electric car that was coming along. And there was no difference in the company between a $30 Tesla stock and a $200 Tesla stock. And of course it’s gone off and it’s totally different today, but it was substantially the same company. They didn’t release a new product or hadn’t solved autonomous driving. I feel that that’s the same kind of scenario with a company like lineage is the lineage is trading at, I don’t know some, you know, some undervalued amount today and in my opinion, and I think we could be worth a lot more in the future. What is the trigger for that? You know, none of us ever know, otherwise we’d all be amazing stock pickers. What I can say is that lineage is very well run. We’re very efficient with how we spend money. We are seeing very exciting results from our programs.

Brian (32:55): And as we continue to do that, I think more and more people are going to get involved. And then, you know, things like share price will take care of themselves, you know, trying to figure out when is that event where all of a sudden it catches fire and everyone’s talking about it. I don’t know. But what I do know is that lineage is engaged in something. That is what I like to say. We’re making cell therapy a reality. So a decade ago, and more people would talk about cell therapy. It would be on the cover of magazines and things like that. And everybody was talking about growing organs. We’re actually a company that is taking those sizzly exciting dreamy aspirations and making them actually happen in human beings today. And I think that’s, what’s required. I think that’s the difference between the futuristic investment and the realistic investment is that we are testing these in people and we are seeing results and we are bringing to bear the promise of cell therapy.

Brian (33:55): We’re ushering in this new branch of medicine. And I’m hopeful, certainly that someday people look back and be like, you remember when lineage was a dollar stock, you know? Right. How could that have been? So there’ll be setbacks. You know, I saw an announcement today of a company called unity that has a lot of incredibly smart investors and they had a huge setback. There will be setbacks. People used to laugh at antibodies for oncology or immuno oncology is like the most incredible thing. And it was a disaster for many years and everyone said, get away from that field. It’s no good. And now it’s probably the most important thing that’s happened in cancer in the last 10 years. I think what’s most important is you get your nose to the grindstone. You do very rigorous high quality science, and then the world eventually comes to you and says, yeah, you did it right. You’ve got something here. That’s going to make a lot of money. And we want to be a part of that.

James (34:45): So for investors that may still be on the fence, what should they look out for with lineage therapeutics? I mean, what type of announcements should they look out for where it’s like, okay, they’re really making some progress here.

Brian (34:56): Yeah. So the data updates are really important. We’ve got one coming up in early November. This is where we get in front of the most critical professionals in our fields. And we say, here’s what we’ve done. And they can beat it up or celebrated whatever. So for the retinal program in early November, we’ll do a data update. And as I said, we had this finding of retinal restoration and it’s just now starting to get communicated among that very austere and critical academic community. And people are starting to say, Oh wow, that’s interesting. Like really smart people have looked at this and are saying it’s real. So our data update on our retinal program is an important event. We have not yet announced all of the data from our oncology program. We announced that we had amended our partnership with a big cancer charity called cancer research UK.

Brian (35:52): And we are now in the driver’s seat on our oncology program, but a little bit later this year, not too long from now, actually we plan on providing an update on our oncology data. So that will be really important. And then the spinal cord program, the clinical study that we’re running is largely complete. We’re just in a followup phase and we’ve been working on the manufacturing. I talked about that at the beginning that the manufacturing is so important. It has to be able to handle huge numbers of patients and you have to have all the consistency and we’ve crossed a lot of milestones and that investors tend not to focus on that as much, but it’s so important to get that right. But we have some other ideas about how we can get back into the clinic. And then lastly, you know, as I say, we have far more than we could ever possibly develop ourselves. And so I think that some of the partnership discussions that we have been having, as we look to find opportunities to mature those into actual transactions, I think that’s going to be really important and validating and expand the breadth of awareness and enthusiasm for our work.

James (36:53): And where can someone stay up to date? I mean, is there a newsletter on your website or anything like that?

Brian (36:58): The website is a great place to go. And in particular, we have a page called our, our media page. And in our media page, we have expert interviews. You can listen to podcasts like this one, we have presentations of oral and video given by myself. We have patient experience videos. There’s a tremendous amount of content. We even have this thing called an IRR minute where we just will pick sort of a random issue and I’ll speak about it. So if investors are asking the same question over and over and we’d feel like we’re not communicating that information well in just 60 or 90 seconds, I talk about it. And so there’s a lot of really fun content and we try to put out information from the company more frequently than others and investors always love to see press releases. And so, you know, we really try hard to communicate with them through that channel.

James (37:48): That’s great to see that you’re so hands on, I think investors will love that. I mean, to hear that you’re so involved, like I said earlier in the podcast, so involved in the weeds and then you’re so involved with investors as well. I think that’s a really good sign of a great CEO. And for anyone listening, I will include a link in the podcast notes on the simple biotech podcast.com. So if anyone is having trouble finding the website, you’ll see it there. I like to end every interview with just one or two fun questions for you, if that’s all right. Sounds great. So what is your ultimate goal with lineage therapeutics or this cell therapy in general? Let’s say 15 to 20 years from now. And you guys have really perfected this. What could be possible?

Brian (38:29): Never gotten that question before, but it’s funny. Cause something just like thunder stormed in my head, I would in whatever shape that cell therapy, transplant, medicine, whatever it looks like in 10 or 15 years, my ultimate goal is that people look back and they say, well, lineage started that now we didn’t really start the field, but I would like this company to be associated with the most significant clinical successes in the field. And we might not think up the best idea or we might not have the best salespeople, but somewhere between the idea and the sales, that is the testing and the proof and the evidence. And that would be my goals that people say, well, you know, the real pioneer here, the people who really bridged the gap from what’s possible to what’s actual, I’d like lineage to fill that gap between the possible and the actual

James (39:20): It’s great again, to hear how passionate you are about things and from a scientific perspective, what could be possible,

Brian (39:26): What could be possible? Well, I believe it’s possible to restore retinal tissue. I’ve seen it with my own eyes now. And I think as we perfect that technology, it’s going to be possible to identify patients with the form of dry AMD early, inject them with these high powered retinal cells and basically stop the disease from robbing people of their site. And I think we’re going to have 2 million people who don’t lose their vision every year in spinal cord therapy. I think we’re going to figure out how best to use this. I think it might be too much to ask for people who are quadriplegics to have the most severe injuries to get back to doing jumping jacks. But I do think we’re going to figure out how to use this and other technologies and combination, and that we will be able to provide really life changing improvements in function.

Brian (40:17): And I think that is, you know, if we never again have people who are quadriplegic and that everybody has some reasonable level of motor locomotion in their upper extremities, that would be amazing. And then an oncology I’m really excited because I mentioned immuno oncology and that’s part of what we do, what people have figured out to do with car T cells. And what’s coming now and, and K cells, I think dendritic cells are going to be an important piece of that puzzle. We just haven’t figured out exactly how to use them in that. That’s partly what lineage is doing, figuring out how best to use these cells. We’ve sorted out how to make this stuff. Now we’ve got to figure out how to use it in a very complicated setting, but if we can do for immuno-oncology, what immuno-oncology has done for cancer treatment, then we are just going to see those oncology incidents and prevalence numbers collapsing. And you know, maybe that’s overly ambitious for everything that we’re working on to work out, but, and maybe all of it won’t be happening at lineage, but all of it to my mind seems entirely possible. And we’re finally approaching the reality through the clinical testing of seeing it happen.

James (41:22): Yeah. It’s an amazing industry to be a part of. And you know, even for me, just as a bystander and watching it, you know, let’s talking to people like you, Oh, it’s so exciting to hear this stuff. So for the final question, what are you most excited about in the biotech world

Brian (41:35): That is in a completely different field than what lineages working on COVID and I’m cheating a little bit because we’re working on it too, but I think it is absolutely astounding how quickly things are moving in, working on a new vaccine. Now it is fraught with distraction and it’s one of these situations where every publication looks equal and they aren’t. There is a ton of garbage there’s misleading stuff. There’s political problems on, on all around us. It is a hot mess. However, the individual people who are working on new therapeutics are massively committed to saving the world. Yes, there’s economic interest. That’s part of it. That’s fine. But I spend a lot of time with the rank and file in our industry. And it is just astounding, how quickly people are deploying resources and moving things forward. And it really does make you scratch your head and wonder how can I be doing my work faster? How can I apply the lessons of coronavirus vaccine development to what we’re doing and find faster, better ways of doing things. That’s what really is just so profound today. Right?

James (42:48): Good answer. Well, Brian, thank you so much for hopping on this call with me. I’m so excited about lineage. I think anyone who’s listening to this should definitely check them out. I’m really excited to see what happens with you guys and I’ll be definitely,

Brian (43:00):
I really appreciate it, James. I thank you for your questions. It’s been a fun podcast for me.

James (43:13): If you got this far, I just want to say thank you so much for listening. If this was all interesting to you, I’d love to connect on Instagram and hear your feedback. I’ll also be posting clips from the latest episodes as well as anything else I find interesting about the biotech industry. You can find me on Instagram/simplebiotech, and if you’re interested in the companies that I’m looking at and the companies that I’m excited about, connect with me on angel list at angel.co/jamesruhle. That’s James R. U. H. L. E. thank you so much and be safe out there.