RARE Daily

Restoring Vision in Inherited Retinal Diseases

July 10, 2024

Inherited retinal diseases are a group of genetic conditions that cause progressive and severe vision loss, such as retinitis pigmentosa, choroideremia, and Stargardt disease. Though they vary in terms of their genetic drivers, they are characterized by degeneration of photoreceptor cells in the retina. Collectively, inherited retinal diseases affect more than 2 million people around the world and are largely without reliable treatment options. Kiora Pharmaceuticals is developing a new class of therapies that can restore vision in these conditions by targeting retinal ganglion cells and enabling them to become light sensing to compensate for the degeneration of rods and cones in the eye. We spoke to Brian Strem, CEO of Kiora Pharmaceuticals, about inherited retinal diseases, how Kiora’s experimental therapy works to treat these conditions, and a recent collaboration that will help drive clinical development of its lead experimental therapy.

Daniel Levine: Brian, thanks for joining us.

Brian Strem: Thank you for having me Danny.

Daniel Levine: We’re going to talk about inherited retinal disease, Kiora, and its efforts to develop medicines to address these conditions. Perhaps we can start with the need. How significant a group of diseases are inherited retinal diseases and what do they include?

Brian Strem: Absolutely, IRDs, which is kind of what we synchronize it to, if you will, are a group of different, usually monogenic, which means one gene has a mutation in it, which causes a defunct protein to be transcribed. And what that really means is patients who have these gene defects and individuals who have them end up usually undergoing some sort of degeneration or decay of their retina. And as most of your audience already probably knows, the retina is the part of the eye that is directly responsible for taking light energy from vision and converting it into the electrical energy required by the brain. And so when you have one of these mutations, what ends up happening is that degeneration occurs. Individuals can no longer make that conversion of light to electricity, if you will, and therefore vision is lost.

Daniel Levine: I suspect it’s apparent to someone when they’re having vision problems, but how easy is it to recognize that you’re dealing with a genetic condition? When there’s vision loss?

Brian Strem: There’s usually a little bit of confusion, especially initially what you see is one of the bigger IRDs, which is something called retinitis pigmentosa. Typically, those effects start to come into play and around the second decade of life—so as a teenager, and what happens as that disease starts, which just having some difficulty seeing in the dark or low light settings, unfortunately, that then progresses over the next few decades to what could certainly be full vision loss. So we know a lot about the progression of the disease. Patients typically present to their doctors because they are just having a tough time seeing. Those doctors then refer them to a specialist within ophthalmology. And that’s where typically a genetic diagnosis comes into play, which is pretty confirmatory as to if it is an inherited retinal disease or not.

Daniel Levine: And how are these conditions generally treated today? What’s the prognosis with someone diagnosed with one of these conditions?

Brian Strem: With the exception of one very small indication called LCA2, where there is a gene therapy approved, the rest of the patients and individuals who have these types of mutations and diseases, unfortunately there is nothing available for them. We as a medical society, essentially train them for living life, if you will, with low vision or no vision. And to me, as someone involved in drug development, that’s just unacceptable. We have some really innovative tools that we are learning about and trying to develop collectively. Obviously Kiora has one that we think is an incredibly promising approach to giving some vision back to people who have lost some of that vision due to these IRDs.

Daniel Levine: Well, I do want to talk about what Kiora is doing, but before we do that, I think it might be useful to just help people understand a couple of terms. What are retinal ganglion cells and what role do they play in vision?

Brian Strem: Certainly. So the retina itself is comprised of specialized neurons, and as we all know, the eye is an extension of the brain, so that makes a lot of sense. The retinal ganglion cells are essentially the cells that make up the optic nerve. So that is going to be the direct conduit from the retina back into what’s called the occipital cortex of the brain, which is really the vision processing center in the brain.

Daniel Levine: Kiora is focused on a class of drugs known as molecular photo switches as a potential means of restoring loss vision. What are molecular photo switches?

Brian Strem: Yeah, that’s a great question and frankly, I asked the same question the first time I heard about that. And so molecular photo switches are small molecules that are responsive to light, and in the case of our molecules that we’re working with, these are molecules that will literally change shape in the presence or absence of light within the visible spectrum. And based on the way the rest of the molecule has been designed, at least our lead molecule, is that they are capable of going into these retinal ganglion cells, which we know stay alive for a very long time, even after the photoreceptors die. And what happens there is it’s able to turn these retinal ganglion cells into light sensing cells by altering some of their molecular channels or what’s specifically called ion channels.

Daniel Levine: Kiara is developing an experimental therapy, KIO-301, which is being developed as a treatment for retinitis pigmentosa, choroideremia, and Stargardt disease. These are all inherited retinal diseases, but there’s not one genetic mutation implicated in each of these and what goes wrong in the eye is different too. What different parts of the eye are affected in each of these conditions?

Brian Strem: That’s a great question. So what we normally see happening in these IRDs in diseases like retinitis pigmentosa, which is actually kind of a bucket of different mutations that can cause RP or diseases that are more specific like choroideremia, Stargardt disease, cone rod dystrophies, the LCA family of mutations. What ends up happening is the photoreceptors, which are those rods and cones in the retina, those end up dying or degenerating. And so what happens when those cells are gone is again, the eye can no longer do that first step of vision processing, which is taking light energy and converting it to what the brain requires. So we do know that there’s a host of different mutations. I mean, I believe the numbers are well north of 100 to 150 at least today, with many more being identified every day as we continue on this path of exploration. But at the end of the day, they all essentially result in a pretty similar ending, which is death of photoreceptors and, depending on which photoreceptors die, will determine if an individual loses their central vision, if they lose their peripheral vision, or if they just completely lose all of their vision. In the case of RP, we know that vision loss typically starts more on the outside, so the peripheral vision, and then as that disease progresses, moves closer and closer to central vision until eventually that is lost as well.

Daniel Levine: It’s remarkable that a single drug can not only address a heterogeneous condition like retinitis pigmentosa, which can be caused by mutations to more than 150 genes, but that KIO-301 has the potential to work across these different conditions. How does the therapy work?

Brian Strem: Yeah, so again, the molecule, it has the capability of changing a cell type—these retinal ganglion cells that we discussed earlier, which are typically not light sensitive cells, they don’t have the molecular machinery to actually sense light outside of a very small sliver of these cells—more responsible for things like circadian rhythm. But in the majority of these retinal ganglion cells, they are conduits. They pass the signal from those photoreceptors to the brain. The way that our drug works, again, it’s injected directly into the eye and there it goes into those ganglion cells and alters the ion flow across some of these specific voltage gated ion channels, and that causes that neuron or that ganglion cell to actually be activated and signal the brain that light is present, or when light is taken away, it allows that cell to revert back to its more resting state, if you will, stopping that signal into the brain. So, in this regard, they kind of work like a light switch inside of a cell, these ganglion cells that are normal.

Daniel Levine: From a clinical trials point of view, are you able to study the drug in multiple conditions at once?

Brian Strem: Yeah, so that’s a really good question because while we want to understand how the drug works, obviously first and foremost, we need to make sure it is safe and tolerable for the individual. So that’s always step one. When you start a clinical trial path, if you will, we conducted what was called a phase 1b clinical trial. So this was our first in human study about a year and a half ago. And in that study we took patients with very late stage retinitis pigmentosa, which again, were not specific to any gene. We enrolled patients with different gene mutations. And what we saw, I can certainly go into a lot of details around it, but first and foremost, it was safe. It did not cause any problems that weren’t already there. But what we really learned at a high level is that the drug was able to give patients some vision back. We were able to give them the ability to perform functions, these individuals that they were not able to do because of the progression of their disease.

Daniel Levine: So, as you sit down and structure additional studies, will it be solely in a single indication at a time or will you be able to do more of a basket trial?

Brian Strem: So, while I think this drug will work, as mentioned before across a lot of these different diseases, we are planning on starting with retinitis pigmentosa, which again is a heterogeneous population amongst itself. It’s probably one of the largest of the inherited retinal disease populations. So certainly a lot of unmet need that we think we can have a direct impact on, especially if the data from our first clinical trial holds, which we would expect it to across these now upcoming clinical studies. And then the idea could be at what point do we expand into some of these other diseases like we’ve listed that are of dear importance to us in choroideremia or in Stargardt disease or even potentially others that are not listed on our pipeline. We think we can impact them. It just really is going to come down to the timing of which we turn those clinical trials on to ensure that again, we take the right, the safe, but also we don’t want to leave patients behind if our drug will help them.

Daniel Levine: And what’s the development path forward?

Brian Strem: What we’re doing now is, actually in collaboration with the Choroideremia Research Foundation, we are going through and doing some final validation work on some novel endpoints, which is what the FDA has asked us to do. Because if you look today, there is no set way of assessing vision for patients who have lost almost all or have lost all of their vision. So we’re working through a little bit of validation work as we speak. And then in collaboration with another partner, a group called Laboratories Théa based out of France, we are going to be kicking off a larger phase 2 clinical study where we will be now injecting the drug into individuals with later stage disease of RP and assessing how well their vision functions across multiple injections over a longer period of time than our first clinical study evaluated.

Daniel Levine: In January, Kiora announced a strategic partnership with Théa Open Innovation, a sister company of Laboratories Théa for exclusive world rights, excluding Asia for $16 million upfront and up to $285 million in milestones as well as tiered royalties of up to 20 percent on sales and reimbursement of R&D expenses. What was the thinking behind the deal? What does it do for Kiora?

Brian Strem: Yeah, so first and foremost, it guarantees that as long as this drug is showing promise and working, that the drug will be funded, all the clinical trials and all the manufacturing that goes into this all the way through getting it to the market and beyond. And that’s really important because while clinical trials are incredibly valuable and we can help patients who are enrolled in our clinical trials, the best way to reach the majority of patients is by having a drug that is approved, and that obviously has to come with a package of data showing safety as well as efficacy. And so the deal itself was incredibly helpful for our company to again, ensure that this drug has a real shot on goal and that silly things like money are not going to prevent it from getting to the market or getting to the patients who need it the most. Kiora is a small company. We are not a lot of individuals. We are very focused and very dedicated folks, but there’s not a lot of us. We are a small company. And so by partnering with a large company that has a full commercial salesforce as well in Laboratories Théa that also helps us guarantee that if the drug gets approved, it’ll be able to get to all of the doctors that have patients who suffer from these IRDs. So again, how we distribute the drug to ensure that patients will get there.

Daniel Levine: Are you seeking a partner for Asia?

Brian Strem: So, as you mentioned earlier, the deal with Théa did not include the Asian territories. Clearly there is a lot of unmet need in countries around Asia as well as the western world and Europe. So while we don’t foreshadow anything with respect to business development, one could certainly imagine that if we could find the right partner, it would be quite valuable to have a third leg to our stool.

Daniel Levine: Around the time of the Théa agreement, Kiora announced a PIPE, this was a $50 million financing with another $30 million in warrants. Why a PIPE?

Brian Strem: Yeah. So, in the case of the financing that we did back in January or early February, we have been talking to some of these key institutional investors who really view opportunities within healthcare and specifically within eyecare as having a good shot on goal from their perspective as well. And these are groups that are going to be our partners as we continue the path forward. They’re not trying to make a quick flip of our stock, being that we are a public company and our stock is clearly traded on the NASDAQ exchange. So, when they found out there was some work done and then they went confidential to understand some of the details, they got really excited by the program and they felt that it was a bet that they wanted to place. So, for Kiora, that clearly added a lot of value by having some of these really good institutional investors join our cap table. But also, what it did is it put enough capital on our balance sheet to ensure that again, we are not going anywhere. We have more than two years of operating capital, so we don’t need to go out and raise more money anytime soon. And it also allows us to invest more into some of the other programs that we also have in our pipeline that we’re working on for patients with, again, a lot of unmet need or underserved retinal diseases. So, the deal with Théa is beautiful because they are going to front the bill on all the R&D costs for KIO-301 as we continue forward. And then the additional capital will again ensure Kiora’s survival at least for the next few years as we think about even potentially innovating new therapies that might help more patients with whether it is these inherited retinal diseases where there’s clearly a lot of unmet need or potentially other diseases.

Daniel Levine: Brian Strum, CEO of Kiora Pharmaceuticals. Brian, thanks so much for your time today.

Brian Strem: Real pleasure chatting with you today, Danny. Take care.

This transcript has been edited for clarity and readability.


The RARECast podcast is made possible through support from the Global Genes’ Corporate Alliance. The members of the Corporate Alliance support Global Genes’ mission and programs, work to meet the vital needs of people with rare diseases, and address inequities they face. To learn more about the Corporate Alliance or how your organization can become a member, click here.



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