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The Blind Life Podcast
Ep. 46 Splice Bio And The Future Of Vision Loss Treatment | Gene Therapy For Stargardt Disease
00:26:56
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A
Hey, guys, it's Sam with the Blind Life. Welcome back to another episode of the Blind Life podcast. We've got a fantastic episode today. My guest is John Tobin. He is the vice president of clinical operations at SpliceBio. SpliceBio is a biotechnology company based in Barcelona, and they develop gene therapies for retinal conditions. Today we're going to be talking with John, learning about his role in the company and learning a lot about SpliceBio's new gene therapy for Stargardt's disease. And stay tuned to the end to learn how you can get involved and possibly change the future of vision impairment. Hey, guys, it's Sam and Rachel, and you're listening to the Blind Life podcast.
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B
This is the companion podcast to the popular YouTube channel the Blind Life.
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Here I share tips and tricks, how.
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To'S, interviews with amazing VIPs in the community and of assistive technology reviews.
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The goal of the Blind Life is to help you live your best blind life. John, thank you so much for joining me today. How you doing?
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B
Very good, thank you, Sam. Pleasure to be here.
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A
Excellent. So before we get to talking about splicebio and learning more about what you guys are working on, I'd love for you to tell me a little bit about yourself, introduce yourself, maybe give a little bit of background about yourself, your role at the company.
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B
Sure, sure. So I've been working in the pharma biotech sector for about 30 years now, so the time has flown by amazingly. And I work in clinical operations, which means that I can cover a whole span of therapeutic areas. So I actually started off working in anesthetics in small little day case procedures, and then I moved on to things like HIV and then antibiotics. And I spent a lot of time in CNS disorders in pain, Parkinson's disease, neuropathic pain, that type of thing. And then about 10 years ago, I actually entered into the ophthalmology world and specifically been working in inherited retinal disease, so rare disease, and using gene therapy almost exclusively over that period to treat those diseases. So. So, you know, really just spent a lot of time over the last 10 years specializing in that particular area.
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A
That's fantastic. Can you tell us a little bit about Splice Bio? In the intro, I mentioned that you guys are based in Barcelona, is that correct?
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B
We are, we are. Unfortunately, I'm not based in Barcelona, so. Yeah, so I'm based in a place called Reading, which is just west of London. Really quite. If you know Oxford or Windsor, that's. I'm near there. And in fact I'm in the Royal county of Berkshire because we share the same county as. As Windsor Castle, where the king. So, you know, he's my neighbor, more or less, but Spiceborough. Yeah, they're based in Barcelona, you know, reasonably small company, about 45, 50 people. We're growing all the time. And we're based actually at the university grounds there in Barcelona. So. So it's a beautiful setting. I get to. I do get to go quite a bit, which is. Which is nice. And, you know, they are a company that's. Or we're a company that is really focused on ophthalmology, certainly at the moment, and targeting these rare diseases where there's a genetic mutation within a gene that is particularly large. And that's quite important. And I'm sure we'll get onto that later as to. As to how Splice bio work and the platform that we're using to treat these diseases. So we're using gene therapy as well. So very much focused in the ophthalmic world, gene therapy and like I say, treating these diseases that have an underlying cause of a mutation within a very large gene. And of course, Stargardt's is one of those. Right. So the ABCA4 gene that codes for the ABCA4 protein is a particularly large one where there's multiple hundreds of mutations within that gene that can cause issues. Splicebar has been around for a number of years, actually sort of five, six years. I've personally been there for about two years now. And the reason why I was brought on is because after all of the preclinical work, the early work that is done in developing these gene therapies, and obviously you get to a point where now you're starting to contemplate and prepare for bringing this into the clinic for the first time. And of course, my experience, as well as experience of some of my colleagues that I've worked with before is very much built around that period. That phase of development is how do we now take this, how do we. And then translate that into the pre. Work that's been done and into the clinic. So how are we actually going to execute that? And that's primarily my role and really what we've been focusing on since the last two years that I've been there. And of course, you know, you may have seen that we've been quite successful in that. In the sense that we've started treating Stargardt's patients with our gene therapy product very early on this year, and we continue to do so.
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A
Yeah, it's it's, it's really exciting. I, I've shared my, my story on, on my channel before and how I was diagnosed way, way, way back in, in 1986. And however, since then, like, like, you know, the doctors at the time were talking about, oh, there's going to be a cure, there's going to be a cure, don't worry. And ever since then, every year people talk about the cure, the cure, the cure. And so we end up, you know, there's actually a term they call it chasing the cure where people just kind of hyper focus on, on this and you, you get to the point after a while where you kind of get desensitized to it and, and well, it's probably not going to happen, so I don't need to even think about it. But honestly, for the first time in my life, there's some really great, exciting things happening within this, this field of, of genetics and gene therapies and all of that. So I'd love to jump into Splice Bio's role in this, but can you share a little bit about what you guys are working on?
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B
Yeah, sure, sure. I mean, just on the back that backdrop as well, of course, you know, there's been, there's been some early successes in the world of ophthalmology in terms of Luxturna and the treatment of LCA2 and the approval of that product and that really just set a platform then that allows us to move forward. There's been a bit of a gap now between, between now and then. Right. In terms of other gene therapies, at least in the ophthalmic world coming through. So, so I can understand the, the, the mindset that you have there about, about the cure, so to speak. And, and it's interesting because the, you know, your story is slightly different from what I hear from a lot of people that, that you're, that you're sort of told, yeah, something's around the corner. So something is around the corner. Whereas a lot of the times we hear that patients are diagnosed with Stargardts and then just sort of told to go away and come back in a.
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A
Year, hopefully happens as well.
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B
Yeah, yeah, which is slightly disappointing, but hopefully you're right. I mean, there's certainly more information that we can provide now and more potential at least for answering some of the questions and whether gene therapy is a good fit for this disease. So I mean, I think the key thing is, is that ABCA4 is a big gene that codes for the ABCA4 protein and just very high level you know, every time a photon of light hits the back of your eye, a photoreceptor will grab that photon of light. And then there's a whole biochemical biological process that then kicks off called the visual cycle. And like every, almost every biological process, there are waste products, there's byproducts that occur as a result of that, that biochemical cycle. And those products need to be, you know, disposed of, otherwise they will build up and they will become toxic and they will hurt cells, they will make cells sick and those cells will eventually die. And that's what the ABCA4 protein does. It's part of the system that clears those waste products away. So, you know, it's. And of course, if that's not functioning properly, then that's when the problems can arise. And typically in gene therapy, what we're aiming to do is then introduce a non mutated version of that gene, you know, a fully functional, properly working copy of that gene. What is problematic is getting the gene into the cells, into those photoreceptor cells. And so we look to nature and to help us identify a tool that can allow us to do that. And you know, a virus does that incredibly well, okay? And so that is the tool that we look to, to help deliver those genes into the cells, okay? Now we modify the virus and in fact, we don't even call it a virus. By the time we're finished, it's not a virus. We call it a vector. And the vector has had the viral DNA stripped out of it and replaced with the ABCA4 gene, okay? The DNA that we want to get into those cells. And then we administer that gene, that gene therapy via a procedure in the operating room or the surgical theater as we'd call it here in the uk. And so that's the basic premise about how we take a gene and we get the gene into those cells via these vectors. Now we said at the beginning that the ABCA4 gene is big. And this, this, this, this presents a different challenge because these, these vectors that we use, they've only got a certain amount of room, okay, to put DNA inside of it. All right? Now if the gene is too big, it just won't fit in. And that's the problem that scientists have had for a long time. And what we're able to do at Spice Spice Bio is, is that we cut the gene in half, okay? So we can create two gene fragments, so to speak, two gene halves, and then share it amongst the vectors, the carriers, so to speak, and then inject both halves into the patient. And now we've got plenty of room within the vector. And in fact we've got so much room we can even add a little bit more DNA that codes for another protein that acts as a sticking glue. We actually call it an intine, but let's just call it a little bit of glue again. That means that once the gene is in the cell, those genes are then codes for proteins for the ABCA four proteins, two halves of them. And then once that those proteins are expressed, those two bits of glue then go looking for each other like a plus or a minus on a magnet. They're really strongly attracted together, they bind together, they stick together and they bring those two halves of the ABCA4 protein together. All right? And that process is called splicing, by the way. And hence that's where the term splice bio comes from. So we all know what that means now. So now you've got a fully functioning ABCA4 protein. So that's the concept and we've seen that, you know, we do a lot of work in the lab and we see that that's what plays out in the lab. And now the job is, right, let's take this into the clinic, let's take that theory, that platform into the clinic and then start treating patients and start to see what this means, what this means to the disease, what kind of treatment responses we're going to get. Right?
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And I guess the ultimate hope is that the correct gene is going to go in and replace the faulty ABCA4 gene.
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Yeah, yeah, well, that's right. In terms of function, of course, the faulty ABCA4 gene will still be there. But what happens? And you, you actually, it gets a little bit more complicated. You add things like promoter sequences that really drive expression of the, the gene therapy of that ABCA4 gene. And it's just a little factory that then sits in the cell for the life of the cell. Okay. Just constantly churning out this really, this fully functional, you know, ABC ABCA 4 protein. That's, that's doing the job that nature has designed it to do.
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A
Best case scenario is this, would this be a one time treatment, Is this a one and done? Or is this, you need to come back every three years and get a treatment.
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No, exactly. So, so I mean, that's the beauty. Okay? So like I say, that gene, that sequence of DNA will sit in the cells for the rest of the patient's life in theory. And just constantly churning this out. So you only need one injection into the eye and we tend to Do. When we get to a point where we're treating both eyes, we'll do it in a few months between each other. There'll be a period between each other so that we can make sure you get a good response in one eye and we're in a safe place with one eye before moving on to the next eye. But, but yeah, it's. The target would be that it's, it's a one and done treatment.
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Yeah, that's fantastic. And ideally, is the goal to regain vision or is it to halt the progress, halt the degeneration and loss of vision?
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Yeah, that's right. So unfortunately, you know, obviously the cells in the situation with Stargardts, they get very sick and they die. And photoreceptor cells, once they're lost, you know, they're not retrievable. So what the goal would ultimately be like you say, is to, is to stop that progression. We know that that dead tissue will progress over a period of time and will just continue to progress. So if we can arrest that growth completely, then that really is ideal. If we can slow the growth down significantly so it makes a difference to the subjects, then of course that's a good outcome as well for the subjects.
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Yeah, I mean, it's going to be great for anyone, but I would imagine especially helpful for those who are newly diagnosed. Maybe myself at age 11, just getting diagnosed, could have gotten a treatment and that would have been fantastic.
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Yeah, yeah. Well, yeah, so, so it's an interesting one because of course, what we do in a clinical trial, which is essentially just a massive experiment. Okay. Is, is we, we need to demonstrate that the, the gene therapy is making an impact. Okay. So now we have subjects who've already lost some areas of retina, and then we want to show that that progression is either stopped or is at least slowed down. Now once we get into the future and the products on the market, then ideally you want to start treating patients who have got very little vision loss. Right. Right at the beginning of this, of this disease's progression and the journey of the disease. And so you can save as much tissue as you possibly can. And, and that could be as early as, you know, in childhood when you start, start. First start to notice changes in vision.
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That's fantastic. Am I correct? I heard a story once that maybe this is completely made up. I heard it on the Internet. And you know, you can trust everything you read on the Internet, but that some like, like it was a, a child or a young person who, who suggested splitting the gene up into two to make it fit better in the virus. Is that completely not true at all, or is any kind of validity to that?
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B
Well, I've never heard it, but I'm going to say yes because it's a good story. Yeah. And kids are smart, right? So. So, yeah, let's say yes. Now, I. In all seriousness, I don't think I've heard that one before, but it wouldn't surprise me.
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No, I picture somebody brought their kid to work that day and they were all standing around, the scientists who were standing around and, well, it's too big to fit in the virus. And the kid's like, well, why don't you split it up into two?
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Yeah, that's right. There's probably all these really very clever scientists all thinking the same thing, but too scared to come up with it because it's a stupid idea. But, no, it's a brilliant idea.
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Well, can you tell us a little bit about your clinical development program?
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Yeah, yeah, for sure. So, like I said, I mean, this is what we've been really committed to over the last few years, and that has come to fruition now. We're actually treating patients, but we approach it slightly differently. And actually it's something. It's a format that I've used for a number of years now, so it's tried and tested, and it works really very nicely. So. So before we even embark on a gene therapy trial, we run an observational trial. I mean, some people call it natural history. It's an observational study. It involves no gene therapy whatsoever. And the reason why we do that is because these diseases are rare and maybe they're not so well investigated or understood as other diseases. And so we want to bring the patients in, get them into a study, and then have them visit on relatively regular basis. And I don't know how often, Sam, you get followed up, but we hear it's every one or two years that people will go and see their ophthalmologists and have some basic tests. We would have our subjects attend our clinics two to three, four times, maybe in a year, so pretty regularly, and start to really start to understand, you know, what their progression looks like, how we're measuring it, how reliably we're going to measure it, and so on. And then once we start to build a profile on this particular population, this particular cohort of patients, then we would introduce the concept of transition them into a gene therapy study. So we have this observational study that's been ongoing now for, you know, about 18 months. It's called Polaris. Okay. Which is the. The guiding star. And it's, it's there to help us and guide us to understand how to take our development program forward. And, and, and so, you know, some of our subjects have been there for a number of months. They, they've come to visit us or visit our investigators rather multiple times. And now we've moved them in to the gene therapy study, to the Astra study. Okay. And that's where we are at the moment. And typically, in an early phase study, you're really looking at safety. You're really just getting the understanding of the dose, which doses should we use, what kind of safety profile we're looking at. And then as the study progresses, we'll start to expand some more and then really shift our focus to, you know, signals of efficacy, you know, how, how this is working within the patient.
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A
Right, yeah. Because there's different levels to all of this, and safety is definitely very much early on in the whole process. Well, if anybody is interested in learning more, what is the best way they can do that? And then also, is this for certain areas of the world, is this only the uk Is this Europe? The US Is involved as well.
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Yeah, yeah. So we certainly have, you know, a lot of investigative sites across. Across the US and multiple sites across Europe as well now. You know, so predominantly patients are being enrolled from those countries now. It's not beyond the realms of possibility, and we see this quite a lot, that there are subjects in other countries outside of those continents, and we'll fly them in. Okay. We'll get to understand, you know, if we can get hold of medical records that just give us some reassurance of, of their diagnosis. And I have to say, the importance of just across the board, okay. In terms of inherited retinal disease, the importance of getting genetically tested is really important. And this is a message that has been going on for years and years and years. And, you know, it still stands true because you've got a real advantage if you've got a genetic report that can tell a doctor, an ophthalmologist, a geneticist, exactly what your genetic profile is. So I'd encourage that across the board. But. And this is where you can take advantage, because we can gather that information and then, you know, we're happy to fly patients across state borders in the US or across country borders and sometimes even across continent borders. Right. To get the patients in the right place to be part of the study. We've got a website, and within the website, there's a little form that patients can Complete and just to log their interest. And we've got a team that will then follow up with that patient. It always helps, actually. Just a little shout out just to put in where you heard about us. And I think we're going to update the website so you can tick a little box. But, but, you know, if you heard about us at the Blind Life, just, just put, oh, I heard about you from the Blind Life Conversation. Right. So we know, we know. Yeah, I thought you might like that one.
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Yeah.
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So we know who's listening and where they're listening as well. So there's a little form there. Or you can just email the team directly and they'll get back to you. And I would say, actually, you know, just. And this isn't just in my experience in ophthalmology, but this has been across the board, you know, when it comes to clinical research, I mean, it's an invitation to people to give their time. Okay. Give their effort to come in and allow us to collect data on them. And they are really consistently the heroes in this environment because without them, we've got no chance. And generations to come have got no chance because we have to create the data to answer the questions. And so people who do volunteer, it is an altruistic act, I think. I mean, they're doing it. We're inviting them to take part and they're doing it for hopefully what will be the good of them, but more often the good of their kids, the good of the generations to come, and just the benefit of medical advancements. So I always want to say thank you to everybody who just shows interest, let alone takes part. Absolutely.
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A
That's a great point. Yeah, you're definitely making history by being a part of this early on and.
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B
Yeah.
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A
And changing the lives for everybody from this point forward. And I love that you said to, to everybody should get a genetic testing because no matter what you have, there's so many different versions, so many different variants, like, I think Stargardt's. Isn't it like 500 different variants of Stargardts.
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Yeah.
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And so this, this company might be targeting this specific variant or this specific range of variants, and you don't know, you know, you've got Stargardt, but which one? So it's really important and a lot of times you can get genetic testing for free. So do some research on that and find out exactly what you have so that you'll know if. If you're eligible for these types of gene therapies.
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B
Couldn't have said it better myself. You know, The Splice Bio approach is we're introducing the whole gene, so it actually doesn't matter which mutation it is. We say it's mutation agnostic. But like you say, in other diseases and in other conditions, people are using gene editing, for example, to just pinpoint, you know, particular areas of the gene itself. So, so you're absolutely right. It is critical that you get that information and, and talk to your geneticists as well, because the, the genetic testing that you may do today, in 5, 10 years time will be far more improved and they'll get even more information. So you, you know, don't be surprised if they ask you to do it again sometime in the future, but. Because it's always getting better. But yeah, get it done as a great system in the US now where you can get it done for free. And in Europe, I mean, it's commonly part of clinical practice. So they don't tend to pay either. In a, in a gene therapy trial, the sponsor that is Splice Bio, we pay anyway, so don't worry about that. So there's lots of different. There's lots there because it can be expensive. I mean, it really can. So there's lots of different options now, which is great.
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A
That's fantastic. All right, guys. Well, you heard it. Splice Bio doesn't care what you have as long as it's Stargardt's. John, thank you so much for sitting down and sharing some of this information. I truly appreciate it.
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Brilliant, Sam. No, no, it's been pleasure, pleasure to get to know you as well over the recent weeks. So good luck with everything.
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If you would like to learn more about SpliceBio and how you could participate in these SpliceBio studies, you can fill out the online form at www.splice.Bio Clinical. That's S P L I C E Period Bio C L I N I C A L. Or you can send them an email at clinicaltrialsplice Bio, that's C L I N I C A L T R I A L S at S P L I C E B I O. I'll also have this information listed in either the podcast show notes or the video description.