Hi, I'm Dr. Eric Daniels, Chief Development Officer at Kiora Pharmaceuticals. I'm excited to share with you today our top-line summary and a bit of our development program around KIO-301, our small molecule for vision restoration in patients with late-stage retinitis pigmentosa. I am going to be making some forward-looking statements, so I do refer you to our SEC filings for additional details. I won't spend too much time on this. Kiora is focused on developing drugs in the orphan retinal space. That just means drugs for the back of the eye for rare diseases. And in particular, we have an interest in inherited retinal diseases, and you'll see why KIO-301 is particularly suited to treat that segment.
You can see that pictorially here, where our intravitreal approach or intravitreal drug has three applications or three indications that we're currently pursuing. Our most advanced is retinitis pigmentosa, the one I'm going to be sharing data about today, along with choroideremia and Stargardt disease. All three of those are inherited retinal diseases, and you can see, while they are orphan and rare, you can see the prevalence or how many people it affects in certain territories and geographic regions throughout the world. Briefly about our clinical and regulatory milestones at a corporate level. You can see that we are indeed quite busy, and most of our output and activity is developed or focused on generating clinical data and advancing programs.
I'm here to share with you our top-line data from ABACUS, and that will soon roll into a follow-on study, ABACUS-2, which we look to initiate in the first or second quarter of next year, and present that top-line data subsequently or approximately a year later in Q1 of 2025. You can also refer to this presentation later and take a greater look or details at our other programs and the timing of that. So really, let's dive into a little bit about KIO-301 and what it does and its mechanism of action. This is an illustration, of course, of your retina, the part of your eye anatomy that is responsible for you to perceive vision.
It's made up of a variety of different cells, and at the back layer, if you will, are these rods and cones. Unfortunately, in inherited retinal diseases like Retinitis Pigmentosa, these rods and cones degenerate, and normally these rods and cones are responsible for sending a signal, which is transferred through a number of different types of cells, including these pink cells called Retinal Ganglion Cells. Those Retinal Ganglion Cells are sort of the end of the train, if you will. Their tail is what is responsible or what makes up your optic nerve, and that leads to your brain, where perception of light, or I should say vision, happens, and the perception of that object or that vision. How does KIO-301 work?
How does it, in fact, restore or aim or look to restore vision? Well, it turns on these retinal ganglion cells in the presence of light. So what happens is that despite the fact that these rods and cones degenerate, you have viable retinal ganglion cells throughout one's life. And 301 has some really interesting properties that it was developed for. So in the absence of light, you can see that by the light bulb on the left, it's not lit. KIO-301, which molecularly is seen on the right, is straight. And retinal ganglion cells remodel when they no longer receive signal or input from degenerated photoreceptors. They put up a protein called, or overexpress a protein called P2X7.
301 has the ability to get inside the cell, and it associates with other channels, in this case, ion channels, that control the flux or flow of ions or current across a particular cell. And in the presence of light, you can see this change in shape, this bend or this movement from a linear orientation to a bent orientation. And the net effect of that is to block flow, change flow, and it actually stimulates the retinal ganglion cell.
So we've taken a scenario, in theory, and this has been borne out and shown in a number of different animal models that have now been published, where despite the fact that you have a degenerated layer of rods and cones, you have a viable layer of retinal ganglion cells, and these molecules, these small molecules, can enter and reanimate the retina, in theory, by being able to stimulate the retinal ganglion cell, which again, the tail of which then makes up your optic nerve and reaches your brain for perception of vision. So Retinitis Pigmentosa itself, as I mentioned, is an inherited retinal disease. It is also a disease with no available treatments, no approved therapies, anywhere throughout the world.
Its clinical presentation is oftentimes heralded by night blindness and ultimately reduced visual field range and ultimately eventual loss of central vision. So just to give you an idea, half of patients with RP really lose their ability or at least their qualification to be able to drive in their late thirties and are often legally blind in their mid-fifties. One of the challenges of the disease is that it's. As I mentioned, it is an inherited retinal disease, but there are certainly a wide variety of underlying genetic mutations. So there are 50-plus genetically distinct subtypes, but that leads to over 150 different types of mutations. So in this case, one of the reasons why we're so drawn to KIO-301 is we are so-called mutation agnostic.
We are not aiming to change the disease or modify disease progression, and there are therapies and development programs that are out there to do that. Our aim is to really restore vision, to take lost vision, and give that back to the patient, depending on where they are in that continuum of vision loss, with RP. So with that backdrop in mind, let's talk about KIO-301 ABACUS- 1, its overview and design. You know, I'll take a step back for a second. I think it's really important when we're talking about first-in-human studies, to really ask yourself: What are the real goals here? You always want to be able to prove your concept. You always want to be able to prove that there's at least a biological mechanism here.
And you're also trying to do that, of course, first and foremost, in the presence of safety. You have a responsibility, and you really want to be able to show that these drugs or your drug in question is safe, and you're also looking for some kind of efficacy signal. You're trying to look for some activity that says or suggests that there is a signal here that is greater than random, or that can't be associated with randomness. Now, oftentimes, most of the time, first-in-man studies are not randomized, and they're not controlled, and that's the case for ABACUS, and we'll talk more about that.
So at the end of the day, our goal is to demonstrate our biological proof of concept and also try to find what are the best ways to measure vision improvement in these patients. And naturally, we want to get feedback from the patients and be able to talk to them and hear from them, "Well, being on drug, what was that like?" And as I mentioned, always looking at safety as an outcome and as an assessment. So when we look at the actual study design, the best way to really think about it is two different buckets of patients. You have two different cohorts. Bucket one, six patients in total. Bucket one involved three subjects, and so there are three subjects in each bucket.
And bucket one is patients who are either no light perception, they're completely blind, and again, have absolutely zero light perception or bare light perception, so they barely have the ability to perceive light. And cohort 2 are patients that have slightly improved, still maintain some level of visual acuity. Clinically, these patients are often classified as either being able to have hand motion or see hand motion, or perceive, or be able to tell you how many fingers are counted. We'll talk a little more about the endpoints and what we actually did to assess these patients. And then along the way, of course, we look at safety, as I mentioned, all the time. So on that note, let's again talk about that.
Primarily, our primary endpoint is to determine safety and tolerability, and our secondary endpoints are a host of exploratory endpoints to determine changes in light perception, look at someone's visual field, which is the extent by which they can see objects, look at their impact on functional vision, and as well as look at what is known as visual acuity or their ability to see contrast and detail. So we measure safety through a number of different standard approaches, and we'll talk and go through each of the efficacy assessments as well. So when you look at the actual number of subjects and their demographics that participated in the study, there were a number of subjects that were very interested in participating in this study, which occurred and took place within two sites within Australia.
There were over 20 subjects that were screened. A total of six were enrolled. There were six eyes treated, excuse me, six subjects treated, 12 eyes. All six subjects and all 12 eyes completed the study. No one discontinued or was withdrawn. And these are just a breakdown of the ages and the genders and the clinical diagnosis, whether they were bare light perception or no light perception. On the far right, you'll see what's called a LogMAR, which is a scale of someone's visual acuity. In this case, it's an inverse relationship. The higher the number, the worse the vision. And so you can see that again in cohort 1, these are subjects with worse vision than in cohort 2. I mentioned our primary endpoint is safety and tolerability.
And so when you look, we are very confident in the conclusion that IVT or intravitreal KIO-301 is safe and well tolerated at the three different doses that we used in this study, namely 7.5, 25, and 50 micrograms. Here we represent or are presenting the number of patients that reported an event or an adverse event, and the percentage of those patients reporting that event within that particular group. You can see most of these numbers are zero, and at the top three, these mildly elevated levels of ocular or intraocular pressure, along with eye swelling and eye pain, are all attributed to the injection of the material itself.
And again, these were all mild, unlikely related to the drug itself, and again, temporarily associated with injection or an intravitreal injection, which is a common and a very routine procedure. So overall, again, we feel extremely confident in our ability to say that KIO-301 is safe and well tolerated at these three doses. So then let's turn and ask ourselves, what about efficacy? How did the drug do? Can we see some sort of signal? Can we tease out some sort of signal that says that this drug appears to be having an effect? Well, let's start by hearing directly from the patients, and let's get a sense from them whether they are able to tell any difference.
Later that week, I went home, back home to Melbourne, and one of my hobbies is bike riding. And we go out bike riding early in the morning. Often leave when it's, you know, first dawn or dark. And as part of that, I put the lights on the bike. And, you know, and on the tandem bike, you know, I've always relied on someone else to say, "Yeah, is the light on? Is it flashing?" And because I had no concept myself. I sort of looked at this light and turned it on and go, "Hold up, I can see that light, and I can see whether it's on or whether it's flashing." And I think that, you know, that was the first time, not only in a clinical sense, but actually, it really goes, "wow, this is really useful.
You walk to the supermarket. At nighttime, I'm walking to the supermarket, and I thought I was in a sci-fi movie. I'm standing I'm looking around, and it was just bizarre because I could... We were walking through the chocolate aisle. I could see everything, and I could see every individual item, which I wouldn't have been able to do at nighttime in with all the spotlights and stuff. And I could see every item, every block of chocolate, you know, all different colors. But the things that were bright were really bright, and the things that were darker were really dark. So everything was so itemized, and, you know, I thought, you know, Dr. Spock was going to be the checkout chick. It was just it was, it was such a bizarre experience, but a good one. So that was a really good experience, too.
Something that was very impressive, the foyer where you come into my unit, it's quite a small area, but again, I thought the light was getting dimmer and dimmer. I'd often look up and try and to see whether I could see the light. Is it turned on even? Then when I saw it, I thought, "Oh, it needs to be made stronger. Well, again, three days after the injection, it was like the whole area is flooded. The light was w ithout me having to look, I could see the light in the ceiling. It was just like the whole little area is flooded. I could even see from the kitchen, I could see the glow from that foyer area.
Naturally, it's great to hear from these patients 'cause we. You know, it provides just such an important context to hear directly from folks that are participating in the study. And of course, that needs to be balanced with the additional data that we do collect. Let's talk about that. The first that I'll bring up is the visual field I mentioned. That's really the space that one sees objects in front of them. So our aim is to evaluate peripheral vision at a basic level, and we use a very established method of doing that called Goldmann perimetry.
When we look at the data, we see that the kinetic visual field, which is measured or expressed in degrees, goes up quite dramatically from a nd you can see that on the left in the total degrees over the course of 30 days in which we follow these patients. Now, I do want to mention this is limited to Cohort 2 or 3 patients, a total of six eyes. This is not surprising. We expect that the visual field for these patients, which is better to begin with, relative to patients that have far worse vision or worse vision. And so we expect them to have a greater response.
And in fact, when you look at their change from baseline, where they came into the study as a group of patients, or in this case, a group of six eyes, and you look at that change over time, we're not intending to see any statistical significance as the study is a first-in-man study and not powered to do that. But naturally, we're encouraged to see that the deltas or the changes are significant at a statistical level at day 7 and day 14. And again, keeping in mind, what we're trying to see here is a signal. We're trying to see whether there's any sense of activity over noise that we can see in a consistent fashion. I mentioned along the way to visual acuity.
Visual acuity has to do with the sharpness, if you will, or the ability to see contrast. For these patients, this is something that is not an easy task because for most, their visual acuity is tested on a traditional chart that you would be familiar with. For these subjects, those charts are frankly just not applicable. There have to be other means to quantify these so-called off-chart patients. There are a few established methods of doing that, and one of them is called the Berkeley Rudimentary Vision Test, or the BRVT. So again, in patients that have better vision, those patients that had vision or a visual acuity, a LogMAR score of 2.3 and 1.8, you saw that.
You can see for them, in this case, a smaller number means better vision or their visual acuity is improving. And when we look at Cohort 2, again, that patient population that had better vision to begin with, we see a reduction in their mean visual acuity or in their mean LogMAR score from baseline at day 30, from 2.1 to 1.8. So that's three patients and three eyes looking at the higher dose. That's actually an important number, you know, achieving that 0.3 level. Oftentimes, 0.3 is associated with a bar of a certain amount of improvement that one wants to see to indicate whether that would be a clinically meaningful change, for these patients.
So naturally, we're happy to also see an improvement in this cohort's visual acuity. Now, one basic question is, well, I'm curious, you know, did the light perception did there did these patients, particularly the ones who were either completely blind or, you know, had bare light perception, could you change, or could you impact their ability to perceive light at a very basic level? So we came up with an assessment, which is simply presenting a series of visual stimuli to these patients. A series of letters are presented on a screen using a rear projector, and we simply ask patients a binary outcome, yes or no, are they able to perceive the light or not?
They can identify, either verbally or physically, whether they take a look and whether they can see that change in light. Again, we are particularly interested in this case in really only cohort 1, the patients with the worst vision, because patients in cohort 2 already perceive light. So it's not surprising that they started at a very high level in terms of their proportion of success or how often they were getting things right and continued throughout the study. But for cohort 1, this patient population in which they either, again, are no light perception or bare light perception, you can see on the left-hand side their change in what's called an odds ratio over time. Now, what is an odds ratio?
An odds ratio is a way to express the strength of association between a given factor and a given outcome. And so if an odds ratio is one, it simply means that there's probably no association between a given activity and a particular outcome. In this case, the activity or the event, if you will, is being on drug. Is there an association between being on drug and being able to perceive light better? So we want an odds ratio greater than one. And just to give you an idea, if an odds ratio is two, that means that there's actually a 100% increase in the odds of an outcome.
So we're starting to see odds ratios, as you can see on the left-hand graph, that far exceed two. So, again, to give you some context here, you might be familiar with diabetic retinopathy. Patients who have diabetes, over 15 years, they're almost guaranteed to have some form of diabetic retinopathy. Their odds ratios are nine. This seems to indicate a high strength of association. You know, try to put that in context, too. What does that really mean in terms of how, what was their proportion of success? Well, they started certainly, you know, below 25% of the time, they were getting that right.
And you can see over the course of the 30 days in cohort 1, this includes 3 patients and all six eyes, that there was a steady improvement, and that improvement, it started to decline a touch, maybe in between towards the end of the 30 days, but certainly was increased relative to where folks entered into the baseline. So fundamentally, it's suggesting that light perception may improve, or KIO-301 may improve light perception in this population of patients. One of the other forms of assessment that we use is to try to recreate or mimic real-world scenarios in which functional vision is tested. We've measured visual acuity, we've measured their peripheral vision, we've measured their light perception.
What about, you know, asking a patient to be put in a scenario that it mimics their environment and ask them, could they identify a door or, in this case, a fake door or a window? Or could they identify someone moving left to right or navigate their way, as you can see in the bottom right, through a course? That's the more challenging task. And what we found was that 301 certainly may improve functional vision on a number of different forms of this test. And again, in an exploratory study, we're really trying to see what tests have limitations, which tests are germane, which aren't. In this case, this is all patients that tried the study, so this isn't cohort 1 or cohort 2.
It's really asking for anyone who tried this test, also called an MLOM suite of tests, is this test valuable? And you can see, we don't see too much of a response in the door location, but that's not the case to the right of that on the walking direction, where there's does seem to be quite a high odds ratio in one's ability to determine whether someone's moving to the left or to the right. Also, the same on the window location, and in the bottom right, the most challenging of which is the high-contrast room exit, that navigation study. You can see, again, their response rate, their ability, their positive response rate. Are they getting it right? Can they navigate without bumping into these foam cubes?
You can see quite a nice increase in one's ability to be able to achieve that, and therefore mimicking a real-world scenario of navigating through one's environment. In addition to not only getting direct feedback, there are established quality-of-life surveys, and we can see when we ask these patients to complete these surveys, in this case, an NEI or National Eye Institute VFQ-25, you see an over three point improvement. From historical other therapies that are out there, a two to four point increase is considered clinically meaningful. So again, we're seeing a number of different signals, all seem to be pointing in the right direction or in the direction that this may improve or may improve, in this case, a patient's overall quality of life.
One of the interesting academic questions that we asked is, I mentioned the retinal ganglion cells, the tail of those cells, you know, are the direct connection to the brain. So we thought, well, wouldn't it be interesting to see whether the brain lights up any differently, whether someone is on drug or not? And we present these patients with a series of visual stimuli, and depending on the stimuli, the colors don't mean intensity, the colors just have to do with the overlapping of a signal. So if you present different stimuli to them, and these are all sections of one's visual cortex or occipital cortex.
And you can see that if you really will look that in the band of day two and day 14, you see an increase in activity relative to baseline, and it starts to taper off a bit by day 29. And we've seen this phenomenon throughout the study and irrespective of the level of visual loss, whether the in this case, the patient on the far left, whose true no light perception through bare light perception, and then a patient who was counting fingers. So this is really, you know, good qualitative evidence, certainly supportive of the fact that we seem to be increasing the signal or to the brain and supportive of cortical activation.
So, you know, I mentioned at the outset, our goal in this study is to look for biological proof of concept, and assure safety, and look for some sort of signal, something to suggest that there's that this isn't random. It does appear that KIO-301 is supportive of that, at this stage. We are looking to take those assessments that we looked at specifically here and have a discussion with the U.S. FDA, scheduled for the fourth quarter, or later on before the end of the year, and counsel with them with respect to whether any of those assessments need to be refined in future studies.
Patients are certainly reporting improvements in vision, and that's consistent across not only their reports, but the data seems to be concordant, meaning no matter, you know, as we depending on how we looked, or I should say, irrespective of how we look, whether it was peripheral vision, whether it was visual acuity, whether it was functional tests, things seem to be all pointed in the right direction, which is a nice signal to have. Now, of course, there are pilot or study limitations. This is a first-in-human study. I mentioned to you again what the overall goals are. This is a non-controlled study.
There are very small sample sizes, so it's really important for us to not make or to come to any major conclusions, except to say that A, this drug appears to be safe, B, it may support reanimation of the retina, and C, most certainly, it merits and deserves further study, in this case, in a controlled randomized study, to be able to tease out further that signal over randomness. And that's what our phase II ABACUS-2 study is about. That will be a sham-controlled, masked, randomized, multiple-ascending dose study at three or four sites in Australia. You can see some highlights here as to how we're going to do that. We are going to continue to use two different doses. We are going to also do a repeat injection.
So not only inject the patient one single time, but we're going to inject them once a month for a period of over three months. And we will then carry out very similar assessments after incorporating regulatory feedback, and we look to again initiate that study in Q1 of next year and report data, subject to pending updates, approximately a year later in Q1 of 2025. So we are very excited about 301 and where it's what it's done so far and where we think it's going to continue to go. I want to thank you for your thoughtful time and attention, and I've indicated our emails below if you'd like to contact us, and very much appreciate your time and thank you again.