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Talking Biotech is a weekly podcast that uncovers the stories, ideas and research of people at the frontier of biology and engineering.
Each episode explores how science and technology will transform agriculture, protect the environment, and feed 10 billion people by 2050.
Interviews are led by Dr. Kevin Folta, a professor of molecular biology and genomics.
A Non-Profit Biotech Model; Gene Therapy for Rare Eye Disease
Talking Biotech Podcast 414
Guest: Dr. Ashley Winslow, CEO/CSO of Odylia Therapeutics
Host: Dr. Kevin Folta
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Kevin Folta: [00:00:00] Hi everybody. And welcome to this week's talking biotech podcast by Calabra. Rare diseases are a challenge for lots of reasons, because when you have such a small population group, it can be difficult to recruit enough people to even begin to formulate a really effective study. And For most big companies, having small patient populations means there's not a lot of potential consumers for a therapeutic that you would develop.
And the cost of R and D is phenomenal, right? It's really high cost. So companies are looking at de risking the Approach to return on investment. And so rare diseases tend to fall off the radar. And sometimes I've been taken up by small companies that we try to promote here on talking biotech because the solutions are usually pretty innovative.
And there's a few examples of that in the archive. But one of the big problems, as I mentioned, is this potential for return on investment, which causes companies to have [00:01:00] to do a lot of market analysis and understand what is the potential. Return for this huge R and D risk that we're taking. But what if there was a different model?
What if the goal wasn't necessarily taking care of shareholders and rather taking care of patients and could a nonprofit model of biotechnology actually be effective? And that's what we'll explore today, looking at the business side of such a model, as well as some of the products in the pipeline.
We're speaking with Dr. Ashley Winslow and she's the CEO and CSO of Adelia Therapeutics. Welcome to the podcast, Dr. Winslow. Thanks for having me, Kevin. I always like calling you Dr. Winslow because I can remember when you weren't.
Ashley Winslow: A long time
Kevin Folta: ago. Yeah, it really is. It's kind of funny. I, I was, I was thinking about this now you, you worked in the lab when?
Ashley Winslow: I think it was is early 2000s about [00:02:00] 2003 is maybe when I started in
Kevin Folta: 2004. Yeah, somewhere in there. And I was, I was standing in front of my class yesterday teaching and thinking, when I started teaching at the university, these folks weren't born yet.
And then, and then seeing you move up through the ranks and things and now being a really senior person at a company, you know, I'm going to grow gray hair because of it, but just for what it's worth dr Winslow was an undergraduate in my laboratory, she did a lot of really nice work at identifying genes that controlled flowering processes in, in strawberry and isolated lots of the regulators for the first time that later would play key roles, so good, good stuff back then.
So thank you for joining
Ashley Winslow: me today. Oh, thanks for having me. It was it, that was the, the start of my scientific career. It was an invaluable experience. I really am grateful.
Kevin Folta: Well, thank you. I, yeah, I am too. I mean, I'm, I'm grateful for, for you, you were, you were probably the fifth of now, 130 undergraduates to move through the [00:03:00] program, so that's pretty
Ashley Winslow: cool.
Wow. That's
Kevin Folta: amazing. It really is. So, let's talk about what you're doing at Odelia. What, what does Odelia or Odelia mean? That's my first question.
Ashley Winslow: No, it's a good question. We get it a lot. And a lot of different pronunciations. So in Odelia came out of actually our founder story. So we, maybe I'll, I'll start there and tell you just a little bit about our founder story.
Cause it's interesting. We have two founders to one is a, a, a father of two kids with a rare disorder. And he came from the business world a successful e commerce business. And so no, no scientific training, but had two children with a rare disorder and as many rare disease parents go about this throne and thrust into this world of science and trying to grapple at what was going on.
And then our other founder scientists by training he, he. comes out of Mass Eye and Ear Institute in Boston and really involved in the development of what we call AAV [00:04:00] capsids or delivery systems for gene therapy. So, so parent scientists kind of thrust into working together in the rare disease world they were, they were frustrated with The researcher not being able to move his science is promising therapeutics forward due to the frustrations in the funding model in that system.
We can go into that more detail and this father frustrated by the fact that we have the science now to deliver, therapeutics to people suffering from rare diseases. But again, the business model was failing in that respect. So the two of these folks came together and Scott Dorfman is our rare disease dad e commerce businessman by training.
And Luke Vandenberg is our researcher from the AAV world. And Luke and Scott just started talking about how can we do better? How can we change the system? And the idea for a nonprofit biotech. Came about, and that was basically the birth of Odelia [00:05:00] Therapeutics and Scott had two children with Usher syndrome.
He still has two children with Usher syndrome. And the biggest component that becomes debilitating later on that's still untreated is the vision loss. Usher syndrome is characterized by vestibular dysfunction, auditory dysfunction, and vision loss in adolescence. And the, while the vestibular and auditory are big components, the auditory component is, is highly treatable by cochlear implants.
Not perfectly, but that, that makes a huge difference. It's the vision loss that becomes really debilitating and quite scary for a lot of patients and families. And so Scott started talking to Luke about how can we treat the vision loss in his kids and, and, and other patients out there. And Luke's specialty area was in vision loss.
And so the, the early days of the company became a focus on vision loss. And they were talking about, what are we going to name this? And so somebody had given Luke, given his background and [00:06:00] vision loss, a St. Odelia, I think it was a candle. And St. Odelia is patron saint of vision loss. So there's no religious aspect to the company, but they started talking about this and it happened to be, I think, very kismet wise, that the patron saint day that they were in Luke's office talking about this, that was sitting on the shelf.
They're talking about vision loss. Scott is just thought this was, you know, interesting connections across the board. So I thought Odelia sounded great. And that is how we came to Odelia. I
Kevin Folta: never knew there was a patron saint for vision loss. Yes. Yes.
Ashley Winslow: I did not either, but I think there might be one for everything out there.
Kevin Folta: Well, let's talk more about this concept of rare diseases. And I understand, you know, sure there's rare diseases that pop up, but for a company, this has to be really a challenge because You don't have the people to study or the organisms to study and at the same time, you know, a [00:07:00] market for any therapeutics you'd develop.
So why are rare diseases worthwhile to pursue?
Ashley Winslow: They are worthwhile because at the base, in my opinion, and I think a lot of, a lot of folks out there, we should be developing therapeutics for the patients that need them. And so. That means that is, is common disorders like different cancers Alzheimer's down to rare genetic disorders.
It, it, we shouldn't, this is an access problem at the end of the day and it's access at the point of drug development. And so while we're working on these big common, more common disorders that, that, that work should continue, but the business model fails. The smaller disorders where there's a much smaller patient population, either when you look at these numbers in the U S or globally, the return on investment.
That drives that business model becomes more [00:08:00] challenging, but at the end of the day, we still have patients who have life threatening disorders. Many of these genetic disorders affect actually two thirds of all rare diseases affect Children and 72 percent of rare diseases are genetic and in a time of when we we've started to develop the science to deliver, deliver genetic therapies, Okay.
We now have the ability to start looking at these genetic diseases and treating them at the source. So I think from a, from a strategic point of view, outside of just the need of patients, we also in the, when we're treating genetic diseases, get to work at some of the, the, the bleeding edge of technology.
And so a lot of this early work on genetic therapies for rare diseases actually. leading the charge for developing that next generation of technologies as
Kevin Folta: well. And a rare disease, how do we define that as rare? [00:09:00]
Ashley Winslow: So there's a few definitions. In the U S we define rare disease by there being fewer than 200, 000 Americans affected.
And that ends up being about 60 people per a hundred thousand people. The EU has a slight variation on that number, and they actually define it by that ratio, 50 people and 100, 000, and I think WHO defines it as 65 people and 100, 000, but you're all in the same type of arena, like different way of counting.
Kevin Folta: Yeah, it doesn't seem that rare though. 50, 50 and a hundred thousand, like, you know, Gainesville, Florida is a hundred thousand, well mm-hmm. 125,000 people. So that would suggest that you would have a 50 person popul patient population for study just in this rather me medium, medium sized town. So it doesn't seem that rare.
So is that really the kind of the attractive size of this is that you do have opportunity to treat a substantial number of people with a less visible disease?
Ashley Winslow: Yeah, it's it depends on the disease. There's [00:10:00] different aspects. So we've I've worked in some diseases that the number can be and ideally actually works right now with a patient group on a disease that has 30 patients in the world which is, is quite rare.
And you can see when you have 30 patients, pharma and biotechs, it had a hard time getting really interested in that. And so some of this starts to fall back on patient groups. Really driving the way. And that's a lot of where we collaborate in the space a little bit differently. But when you look collectively across rare diseases, so you have those end of ones, we now call them one patient known worldwide.
You have those 30 patients worldwide for another disorder that can walk up to much more common rare diseases. And there's examples of those, but you have a, you have a wide spectrum and the business model. doesn't fit for many of those. We're starting to see interest in changing that business model and [00:11:00] having that work for the more common, but we're still struggling with those fewer, but in totality, if you look at the aggregate of rare diseases for, for all people living with rare diseases, that is actually one in 10 people in the U S when they've done those calculations.
So, If you talk about the social impact, the health impact, there's a massive impact on society from leaving rare diseases untreated. And so there's that individual need, but there's also that society, societal responsibility as well.
Kevin Folta: And so is that a big part of your company to identify these rare disease groups and then maybe serve as a backbone that has the expertise to help them navigate drug discovery and, and, and regulation?
Is that part of what what your company does?
Ashley Winslow: Exactly. Yeah. So we have two sides of the company. We work very traditionally as a biotech. So the nonprofit biotech side of how we characterize ourselves. We have a pipeline. [00:12:00] We have two gene therapies currently in development. We, we. Each of those has partnerships, really strong ties to patient groups or the patient community, depending on how they're organized.
But we also, on the other side of the company, work through what's called bridge solutions. And that's where we bring that expertise, our internal expertise, as well as the networks we work through to directly to groups working on their own pipelines. I'd say most of our collaborations have been with patient groups within that space who are driving their own drug development efforts.
So they're, they're raising funds and they're investing in maybe academic based research on trying to understand the biology of the disease or discovering new therapeutics. Sometimes that matures into a full blown drug development effort. And sometimes they're building their own companies, which has just been truly amazing to see.
But as you can imagine, if you're thrust into the world of rare diseases, you have a sick kid, let's say. And you [00:13:00] have no background in science. This can be incredibly daunting. And so what we're trying to do is take our learnings and our expertise and our network and make that available to these parents, these patients, these families, these patient groups.
Who start with very little understanding of that landscape because it's not their career training. And making that available and making it accessible to those groups.
Kevin Folta: That's really exciting. Kind of being the hub on the wheel where you're able to provide that backbone. to support the efforts of these other groups.
I mean, that's really a cool model. But the other side of this is that you kept mentioning non profit and in the days of, you know, Wall Street you know, loving biotechs and all this good stuff. Tell me more about the non profit nature of a biotech company.
Ashley Winslow: Yeah. So we are a 501c3. And so it's the basis of that really comes from the founder story that I, I spoke to early in early days, it's, [00:14:00] we have the science of technology to develop, you know, it's scientists have a hard time with the C word cures or curative, but we really are looking at having a massive impact on these diseases through genetic treatments.
Some will call them a cure. And given the small patient population, we're fundamentally challenged when you look at that traditional business model by the return on investment, and it can be self limiting. And so Scott and Luke, when they talked about this, discussed this in early days, they really thought in order to keep The mission focused on the science and advancing these technologies in the rare disease space, we had to be formatted as a non profit and it's so that affords us a lot of advantages in the space to operate differently.
So we have the ability to focus on 3 guiding principles and that [00:15:00] are 3 questions around each of our drugs and development. Are they safe? Are they effective? And do we have the available and appropriate technology to treat this disease? We don't have to go to that market assessment where a lot of programs begin and do the assessment on what's the market for this product?
What's that? What can we sell it for? What's the potential return on investment? Don't get me wrong. I worked in Big Pharma and I loved it. It was a wonderful experience and very eye opening. There's nothing wrong with that thinking because it does drive a lot of innovation, but it has failed in the rare disease space as a model.
So we, there's a lot of different approaches that are starting to emerge. Our approach as a nonprofit allows us to focus at the core on safety, efficacy, and available technology. But it's also not without its challenges. As you can imagine, raising the capital from a nonprofit space to drive these programs forward can be challenging.
So it's the financial model is, is a little bit more [00:16:00] challenging, especially in early days. But I do think we have a strategic road map where over time and we, we are able to tackle that bigger challenge. I'm happy to talk about that in more detail if that's of interest as well.
Well,
Kevin Folta: it is of interest because it makes me think, all right, this is a great idea.
I love, I'm sitting here thinking of ways that I could do this in plant breeding. You know, how do you do run it as a 501c3 where you can generate maybe something that can help a different market rather than a thousand acres. Maybe how do you just get small farms to have be more profitable? You know, this is going through my head as we talk.
So where does the capital come from to run the business? Yeah,
Ashley Winslow: so it's a good question. I'll talk to speak initially about the general concept. So we have three primary financial pillars and I'll talk very transparently because I think about our financial situation. I think it helps others think through how to apply the model and how to think about it.
Because there's things I would have loved to have known you know, in earlier days that I feel like we have a [00:17:00] better understanding at the stage we're at now. So we were founded in 2017. Really? Got running. I would say 2018, 2019 is when I joined. And our, our three pillars today are licensing or what I call a bigger bucket business revenue, and I'll come back to that in a second.
Traditional philanthropy. Donations and we can, we can talk about that as well. And then under bridge solutions, we structure that as a fee for service right now, that's heavily subsidized when we work with nonprofits and patient groups. We're actually operating under, under the real rate and we're hoping over time that our, our fee for service structure with for profits can help underpin and subsidize that piece.
So we can continue to work with nonprofits and other patient groups at an accessible price point. With regard to our early days. So in 2019, we did have a licensing deal with a company [00:18:00] at that point that that gave us our initial runway. And that's important for for a nonprofit. When you start to walk into the space, when you're a new entity, and you're in that startup phase, you operate in many ways, just like any other startup in the space, you have to have ideally an initial revenue source while you're working on the sustainability model.
And so for nonprofits, oftentimes that is through driving philanthropy donations, maybe early grants. We had the ability when we were founded, we were seeded with some intellectual property coming out of Luke's lab. And pharma.
And that's model still model. We subsist on. It's, it gave us that initial licensing revenue, gave us our initial runway it allowed us that ability to have the revenue to build a sustainable model, [00:19:00] which we're still working on it. It is a challenge for nonprofits because you are, you're challenged with convincing people that your mission is truly worth investing in, but in a way that they're not, That society is going to gain from it, not necessarily the individual in a financial way.
And so that's a very different prospect. We, I think the early, early days of Odelia right now, what we're focused on and what we're starting to emerge out of is the, the model is the hope that we can de risk our rare disease programs to a stage that we can attract investment from them. The traditional biotech pharma or our VC landscape and get them interested in working on rare disease and committed because once you move into clinical trials, they're incredibly expensive.
Now, what our hope is, is that. One day we are at a a point that we can [00:20:00] bring those programs forward and not reliant on that landscape, but anywhere we can attract anyone to work in rare diseases, we're not opposed to for profits working the space. We want to get them interested in it. But we also want to build a different business models when that doesn't work.
But our hope is one day that we can get to a sustainable place where we have enough funds to invest in these programs to take them through the very expensive clinical trials to approval. And I think we have ways of getting there. So early days. licensing revenue as a potential, we stay tied to our programs to ensure that they're being stewarded properly and that if the program is ever jettisoned or stalled, it comes back to us and we can ensure it keeps moving forward, which is a big problem as you know, and, and, and pharma.
But there are now incentive programs. Business incentives through different government systems. California has a great one through CIRM, [00:21:00] and that's C I R M, and I'm blanking on the full acronym at this point in time, but they give funding for California entities to fund these early stage programs and companies and clinical trials.
And so we're starting to look at those types of programs. There's also or for drug designation and rare pediatric disease designations, which are first asset, their gene therapy and development does have that designation. When you go to the point of approval, you get what's called a priority review voucher.
And the value of that ranges, if you wanted to turn around and sell it, which you can from about 80 million to 110 million. So you can start to see if we can bring these programs into that longer phase and fund them to that longer phase. There starts to, there start to be ways that we can bring money back into the early side of the company and invest in our next stage.
Of programs, but there's a, there's a longer, you know, [00:22:00] runway to walk in that walk. And it's, it's a longer term goal.
Kevin Folta: And maybe just kind of a personal point here is you, you are CSO at other companies. You've worked in kind of the academic corporate straddling there for a long time. And was that what attracted you to Odelia?
Was this for this non for profit model?
Ashley Winslow: Yeah, I've I would say that the thread that kind of drew me into a deal is I've worked in the rare disease space for a long time. I've worked in the world of looking at genetic underpinnings of disease and asking the question of how do we develop that into better therapeutics?
That naturally segues into rare diseases because 72 percent of rare diseases are genetic. And this has really been the test bed for these genetic technologies, which is, it's been really interesting to see up front and center. And I've worked in academia, like you said, pharma worked in between and worked with a lot of patient groups as well.
[00:23:00] And I think the, I think the underlying kind of guiding principle for me also, it's just, I can't resist the challenge and seeing and working with a lot of these patient groups and a lot of these programs in pharma and seeing. Then not stalled because of the science, but stalled because of the business model.
It was, it was, it's a challenge that was hard for me to resist. It, it, it's been incredibly inspiring and fun to, to, to come up against this challenge and try to figure out how do we do this differently and can we make this work and, and, and how do we get people excited about it, but it, we're really starting to see that momentum grow and, and.
It's, it's incredibly rewarding, but it will continue to be a challenge. I think it, but if, if you thrive on challenges, I encourage anyone to think a little bit differently and outside the box and challenge that traditional business model where it falls short, it's, it's been an incredible experience.
Kevin Folta: Well, that's really cool. So we'll talk [00:24:00] a little bit more about challenges and Dr. Ashley Winslow on the other side of the break. This is collaborates talking biotech podcast. We're speaking with Dr. Ashley Winslow. She's a CEO and CSO of Adelia therapeutics. We'll be back in just a moment. And now we're back on Collabra's Talking Biotech podcast.
We're speaking with Dr. Ashley Winslow. She's the CEO and CSO of Odelia Therapeutics. And before the break, we were talking about the four, the non for profit, almost got that backwards, the non for profit nature of, of Her company and some of the unique challenges. But the second half, I'd really like to focus on the technologies themselves and specifically the pipeline and some of the solutions that you're working on.
But you mentioned before challenges and it really brought to mind something I haven't thought about in a long time was when you were going from undergraduate, a university of Florida to PhD, and you had your sights set on Cambridge in the UK and a certain lab [00:25:00] to, to work with. to work on aspects of autophagy and Alzheimer's disease.
And you were on fire about this. And you actually went there without an assistantship because they didn't, he was, you know, didn't have one to offer at the time. And you basically said, I'm going to go make this work. And then four years later, I got a bound copy of your dissertation in the mail. So someone who, someone who is not averse to making it work and bringing along some success.
So it just kind of came to mind now. I still have your dissertation, by the way.
So let's dive in and talk about the actual technologies themselves and what's being done. It sounds to me like you're doing a that these are current therapies are focusing on disorders of the eye and. Gene therapy solutions. Is there a reason, and this has been true, I guess, with other gene therapy solutions in eye disorders typically metabolic [00:26:00] disorders of retinal cells.
And why is, why is the eye particularly amenable for these kinds of gene therapy applications?
Ashley Winslow: Good question. And it's the, you know, besides the, the initial success with luxterna. So that's the first approved. Gene therapy or in vivo gene therapy, there's kind of a difference there between ex vivo and in vivo.
So this is direct genetic gene delivery into the eye. So the initial success, I think, success for success and interest. And so that drives a lot of people to the field saying, Hey, you know, look, look over there. That person can do it. You know, I can too. They've laid the. The path outside of that, the, the, I really, it has some very unique characteristics that lend itself to gene therapy from a scientific biological perspective.
It's relatively separate from the rest of the body. So when you deliver something into the blood, it goes everywhere. That's the point of blood is to, to get a lot of different [00:27:00] places very quickly. So when you're trying to deliver gene therapies. Systemically, it can be a challenge for a few reasons because you have to deliver large doses and that becomes a manufacturing problem and a cost problem.
Gene therapies are pretty costly in the spectrum of manufacturing to develop. So smaller doses are ideal. And the eye, given it's relatively Isolated from the rest of the body behind different barrier systems becomes a very, very small organ to deliver effective and therapeutic levels, doses of gene therapies too.
So there's a, there's a cost perspective, but there's also an immunological perspective when, when the early days of gene therapy, they're there and there still continues to be their immunological effects. You have to be mindful of and, and monitor for. These are experimental technologies in the initial days of testing.
So especially the first time we start [00:28:00] introducing these into patients in a phase one trial, there's a lot of interest in understanding, is there an immunological response? And so when you have an isolated organ like the eye, instead of that systemic example of delivering to the blood, You can limit some of the effects if there's an immunological response to one organ system, to one area, and also higher doses often drive larger immunological responses.
So that isolated nature of the eye, it allows access, easier access than, let's say, when we're doing gene therapies for the brain, which worked in that area, and that could be a real challenge. Brain is somewhat isolated behind the blood brain barrier, but you can access all parts of the brain very easily.
The eyes relatively accessible. We can visualize it as well through some, some of the, the ophthalmological technologies we [00:29:00] have. We can sometimes look at the direct effects on. And monitor, you know, retinal cell layers. We can look at those in a, in a human patient. We, we, we don't have to, to wait for them to, to pass away or succumb to a disease where we do some areas to really look at the direct effects.
Sometimes we can monitor those in real time. So it's an access the advantage really with the eye.
Kevin Folta: And let's talk about some of the diseases that you're working with. So what is Leber congenital amaurosis?
Ashley Winslow: So this is an early blinding disorder. And so usually LCA, as we call it for short is a group of different genetic disorders.
So we are specifically working on LCA six and that links to is really tied to. mutations in the RP group one gene. So LCA is generally as a class of diseases affect children, [00:30:00] very young LCA six, many of the patients we work with, they had affected vision often from birth. So oftentimes patient parents, excuse me, we'll Realize this in the first few weeks.
It really starts to become measurable later on when you have fully developed vision and babies that the doctor really starts to to be able to see that there's a problem. The parents usually have recognized this for a while that their child's not tracking when when they should. And that's a big milestone component that parents look at and then or look for or maybe their eyes.
Start to kind of go back and forth a lot, something called nystagmus. And so there starts to be unusual behavior. Oftentimes these children do have, these children do have a formal diagnosis by the age of one or at least before the age of three years old. And it's, there is a plateau [00:31:00] phase with the progression of LCA.
So severe vision loss early on, and then sometimes that can be steady state for a while, but there might be some retained visual vision. Is retained. And then oftentimes in adolescence, this starts to drop off again. So this is, we do think that this phase, there's a long phase in a pediatric population that's highly treatable.
And that may even go into young adulthood. But just for clarity, so RP group one mutations do track with three diagnoses, usually LCA6, CORD13, and then sometimes juvenile retinitis pigmentosa. And so you have that, that interesting biology where one set of mutations is recessive. So you would have homozygous or compound heterozygous mutations in the RP group one gene.
Can track with slightly different manifestation. So we've had a really interesting layering of your diagnostic practice. [00:32:00] Maybe different ophthalmologists see things slightly differently and call it a different thing. Or, or, or truly, we do think some of the biology lends itself to a later onset of this vision decline.
Kevin Folta: Yeah. So this is a, so this is maybe something I don't understand about this. So did you say LCA, LCA six, there is other versions of this also potentially. So other, and I don't know this for sure. So this gene that is being targeted here, the mutation that's occurring is happening in what gene?
Ashley Winslow: RPGRIP1, R P G R I P
Kevin Folta: 1. Okay, R P G R I P 1, R P GRIP 1. And has other gene therapy been done for other states? Is this the same disease that occurs in Briard dogs?
Ashley Winslow: So there, interestingly, there ends up being a lot of. Mostly I would say canine models, yeah, dog models for vision loss. And I think that, I think largely [00:33:00] much of that is due to inbreeding and also just because pet lovers love their dogs so much that they take them to the doctor and say, you know, help me figure out what this is.
So you end up with because of these breeding programs highlighting some of these. So there are. There are RP group one canine models and I can't remember exactly what breed. I think there might be two.
Kevin Folta: Yeah, it just was something I'm doing kind of a deep dive here for, for going to actually go back quite a bit.
I'm kind of remembering this, that there were a number of gene therapies that were proposed for different blindnesses that occurred that were maybe in the RP 65 gene that were the gene that was the gene that. Catalyze the conversion of the beta carotene to pro vitamin a with that cleavage down the center.
And so this was, this goes back always in my brain, but it sounded really familiar as you were speaking about it. So this is a different gene than RP 65.
Ashley Winslow: Yes. Yeah. RP 65 does cause a form of LCA, but it's a different number and, and [00:34:00] I don't, I'd have to look and see what number we're up to, but we're in the teens at least of different LCA days.
All. Underpinned by a different genetic mutation, but it's, but similar, somewhat similar manifestation and, and how the patient, how young they might be or the progression, not all exactly the same. But within the same umbrella group.
Kevin Folta: Yeah. That's, that's, that was a deep dive in my brain. Jeez. I can't believe I didn't remember that.
So the the Actual therapy itself is a gene therapy, which is delivered by virus. And so can you tell me a little bit more about the viral vector and how that is used to deliver the appropriate corrected copy of the gene?
Ashley Winslow: Sure. So we are using AV technology. So done associated virus. And basically this system for delivery is hijacking common viruses and I'm oversimplifying, you know, a little bit here just to kind of convey the delivery [00:35:00] mechanism, but you're basically hijacking.
Viral systems that have a propensity and very well evolutionarily geared to Deliver their payload into human cells so we can hijack these systems in ways that we remove some of the Component remove the components that would cause disease or ill effects in humans and then load them up with our gene therapy payload.
So, so in this case, we have patients have a loss of function mutation in rpGRIP1 inherited. They have those loss of function mutations inherited from both parents and both copies. So they don't have a functional rpGRIP1 protein. So we basically hijack this AV system to deliver a functional copy of rpGRIP1 into the retinal cells that we're targeting.
And so that would be an injection into the retinal layer on the back of the eye[00:36:00] what we call photoreceptor cells, what we're primarily targeting. And the, the AV that we're specifically using, there's a lot of different types that are used to deliver to different parts of the body. And that's dependent upon the biology of these viruses.
So, as you can imagine, you know, when we get viruses, they might affect different cells differently, and that's why you have different symptoms and in different parts of the body. And in this case, we are using ANK80. That's the AAV capsid name that we're using that was discovered in Luke Vandenberg's lab.
And some of the IP or intellectual property that, Odelia was seeded with. And it has, Angiidae has some unique biology for, especially in the retinal space, it has some advantageous biology compared to other capsids. It, it, it seems to spread a bit further and deliver in a more targeted way to different cells within the eye that we can take advantage of and, and really.
optimize the therapeutic and hopefully lower the [00:37:00] dose for delivery into patients.
Kevin Folta: And so where is this product in the pipeline right now? And where have you seen evidence of it actually working? So
Ashley Winslow: we, right now, our first program in our pre grip one, this LCA six program is in late, what we call late stage preclinical testing.
So It has been through the initial efficacy testing in mouse models of the disease, and so we've shown it's effective. We have, right now we're moving into manufacturing the gene therapy at scale. And so that's an interesting process in and of itself, and almost kind of separate from your usual disease biology and safety testing but that will allow us to move into toxicity testing as our last and final phase of preclinical.
So we're hoping in the next year to manufacture our, what we call our tox batch of the vector, and then move that [00:38:00] into formal toxicity testing to really assess that safety question. So we we've answered, do we have the genetic technology? Yes. Is it effective from what we've seen in mice? Yes. And we have done some earlier preliminary safety testing and what we call feasibility testing just to make sure we can deliver it to the right place for the right period of time.
At the right period of time. So gene therapies, we really think of this as longer term hopefully permanent but we're, we're not sure really where the science is going to land. We need longer trials and, and these first programs like Luxterna and Zolgensma, the first gene therapy programs.
We'll get a much better picture of how long these gene therapies last. Is it decades? Is it multiple decades? Is it forever? So that's a longer term question outside the scope of this program, but that initial feasibility and safety short term testing is done and it looks very promising. We're getting RP group one.
Delivered into [00:39:00] cells in the eyes. We're able to see that expression and we're excited about really bringing that to formal toxicity testing in the next
Kevin Folta: year. Very cool. And the other one you're talking about is Usher syndrome. And you mentioned earlier, this is something that involves the cochlea.
It's a vestibular issue for, so probably affects balance and I, a visual issue. So is this something that so tell me first about the gene that is affected here and what it does.
Ashley Winslow: So there's different types of Usher syndrome similar to LCA. So a lot of things fall under that Usher umbrella. There's different types that affect the visual system or the, the impact on, on hearing can be at different levels or onset can be at different points in time.
So for Usher, for the Usher syndrome type we're talking about, we are focused on delivering a functional copy of the USH1C gene to patients photoreceptors and, and maybe some other cell types that really take [00:40:00] advantage of that ANK80 bio, unique biology. We're right now still working that out with a set of collaborators in Europe that really know the fine biology of USH1C.
USH1C profound, causes profound. Deafness from birth. Many patients go on to have cochlear implants implanted within those first few years of life. And then they'll go on to start to have visual disturbances in, in early adolescence or as older children, you know, we're starting to really understand that better now because we're, we're starting to have these genetic diagnoses earlier.
So, so clinicians can start to track. The onset of that visual disturbance before it starts to happen. So we're really starting to have some finite detail to pinpoint when, when we start to see the first functional impact as well as anatomical impact. And so we're, we're working, as I mentioned, [00:41:00] with a group of collaborators out of primarily Europe who have expertise in H1C biology, and we are also working with a, a pig genetic model that they developed because unfortunately we do a lot of mice.
In the drug development world, but the mice don't seem to have the visual disturbances. And so we're, we're hoping to have some exciting data in in this pig model they've developed in the next year or
Kevin Folta: so. And you mentioned that this is a gene therapy. It's going into the. I predominantly, but does this also correct the auditory and vestibular issues?
Ashley Winslow: So that would have to be going back to the, the, I, the advantages of the eyes, it's relatively isolated. So we would have to do a separate targeting in the ear or in the vestibular area. So we're not working on that right now because the cochlear. Plans seem to, to, they're not perfect, but they treat a lot of the auditory component and allow [00:42:00] these patients to, to interact auditorily.
I think what I'd love to see is if we had success in the eye is, is possibly come back to. That question later on, or maybe work with there's some really great auditory gene therapy companies who might be interested. So maybe we could collaboratively work in that space. There's also some interesting biology where it might be a different isoform that's working in the ear.
And so we'd have to look at that in more detail. Yeah.
Kevin Folta: That wouldn't, that would explain the mouse model possibly. Yeah.
Ashley Winslow: Yeah. It's, it's part of the suspicion is why we have different effects in different animal systems.
Kevin Folta: Well, you just described two different gene therapy approaches and that seems to be because the company's rooted in this vector delivery system.
But do you think Odelia is going to be working on maybe more traditional approaches and other types of therapeutics?
Ashley Winslow: I think that's, that's definitely in our future. And so the, the focus on vision loss initially in our pipeline [00:43:00] again comes back to our founder story. The, the, the, the, the IP we're initially seated with kind of drove us into these diseases.
Luke's lab was initially working on the, the groundwork for the RP group one program. And our other founder actually approached him about working in Ashburn C after I'd been with Odelia for a bit, because I thought, you know, there's some, we didn't understand all of the biology, but we understood enough that we could start, I think, making inroads in this space.
And so we'll, we'll see how that pans out in the next year. But Our DNA really is rare diseases as a company. And so I think after we'll have a lot of expertise in the vision loss space and will continue to be committed there and bring those programs forward. But I think we'll look, we will look at different opportunities and other rare diseases outside of vision specifically.
As far as the, the platform, the therapeutic platform, we are, we, we call [00:44:00] ourselves agnostic. So we're building up that base in the gene therapy world that will continue to grow, but we look at opportunities as they come about in our bridge solutions program. We're working with a few gene therapy programs actually know at the moment we are not working with any vision loss disorders.
All of those are either. Neurodevelopmental we have a few overgrowth disorders, and they run the gamut of gene therapies repurposing screens ASOs, or antisense oligonucleotide approaches, silencing approaches, so. I think those will continue to grow. Some of those will stay with those patient groups and will continue to support their efforts, but there might be opportunities that arise and might, there might be a, a bigger partnership where maybe those programs in the future come into our own pipeline as well.
Kevin Folta: Well, Dr. Ashley Winslow, it's so nice to call you Dr. Ashley Winslow if, if listeners or a generous philanthropist wants to find Odelia, where would they find you [00:45:00] online or social media?
Ashley Winslow: Sure. So we you can find our website at odelia. org, O D Y L I A dot O R G, and you can find more information about.
Our mission, our pipeline bridge solutions as well as how to donate there and and also check out if you're interested. We've recently launched the Odelia library, which is this is where we're trying to bring our learning through bridge solutions. As well as our pipeline also to a public space where people can learn from those resources.
We just launched it in April. So it's early days, but we will be building that library over time. So feel free to check check it out. And then we're on most of the usual social media platforms. These days. You can either find us as Odelia therapeutics. Two words or Odelia TX one word depending on the platform and we're on LinkedIn Instagram Twitter Formally Twitter, I guess X these days [00:46:00] and I think we're newly on Facebook as well.
That
Kevin Folta: always be Twitter to me
Ashley Winslow: X's Two general and generic. I got it. I don't know. I don't know what to make of it. Yeah,
Kevin Folta: it's I, I wanted to start quitter a long time ago. Q W I T T and then just be all the people who used to be on Twitter. It's high time for that. So maybe I'll do it. Well, anyway, well, Ashley, really, really, really nice to talk to you.
Thank you very much for joining me today. And let's do this again as the pipeline progresses, because I love the model and it's awesome to see rare diseases being treated.
Ashley Winslow: Would love that. Thank you, Kevin.
Kevin Folta: And as always, thank you for listening to Talking Biotech Podcast. This is a great example of how biotechnology can be used to solve problems for people and people who maybe would be disregarded by a, by the typical large pharmaceutical model.
And here's an idea of not just Innovation in the space of [00:47:00] biotechnology to solve a problem, but innovation in the business space to find different ways to fund discovery, to take care of people. I think it's totally cool. So this is the talking biotech podcast, and we'll talk to you again next week.