Good morning, thank you for joining us today to delve into our gene therapy pipeline with a focus on our earlier-stage programs. As a reminder, this event is being recorded. Before we begin, I'd like to remind you that during today's call, we'll be making certain forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements. Please refer to our annual and quarterly reports and our other SEC filings available on our website. Any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so, even if our views change.
A recording of this event and the accompanying slides will be available in the events section of the Opus Genetics Investor Relations website later today. We have a really terrific lineup of speakers and are really grateful for all the key opinion leaders joining us today to share their expertise on the treatment of inherited retinal diseases, including target indications for Opus. For reference, you can access speaker bios on the right side of your screen or via the button in the top right corner. Today's agenda is divided into two parts. In part one, we will provide a brief company introduction and scientific overview. One of our KOL guest speakers will discuss each disease, followed by a summary of our scientific approach for the corresponding indication.
We will review our clinical development strategy and approach, followed by our first Q&A session on these programs that will be entering the clinic later this year and into 2027. Please note that any time during our presentation today, you can submit a question using the Ask a Question button on the top right corner of the screen. In part two, we will provide a brief summary of the clinical trial data from our lead programs, LCA5 and BEST1. We will highlight the recent epidemiology work we commissioned to better inform the disease prevalence of our seven current indications. Finally, we are excited to host a panel discussion with several industry experts to discuss patient recruitment and retention in inherited retinal diseases. We will open the call back up for questions.
I'd now like to turn the call over to Dr. George Magrath, Opus CEO, to kick off our program.
Thank you, Ben, and good morning, everyone. At Opus Genetics, we're focused on accelerating groundbreaking gene therapies for inherited retinal diseases. We're advancing a portfolio of seven AAV gene therapy assets built on validated science and a proven delivery approach pioneered by our co-founder and guest speaker today, Dr. Jean Bennett, whose work led to the first approved IRD gene therapy. We hold first-mover advantage across multiple indications supported by broad IP protection, orphan drug exclusivity potential, and rare disease regulatory pathways that offer flexibility and potentially accelerated approval. Our approach emphasizes streamlined timelines, capital-efficient development, and the ability to progress multiple clinical programs in parallel. We are fortunate to collaborate with leading scientific and clinical innovators in gene therapy, many of whom are here with us today.
By building a portfolio that spans multiple rare retinal diseases, we believe we can capture a meaningful share in a multi-billion-dollar market and deliver multiple approved therapies for patients with severe genetic eye disorders. As you will hear today, our validated scientific approach and early clinical success give us strong momentum as we expand into our next group of promising programs. We're currently targeting seven inherited retinal diseases caused by genetic mutations. As you think about the indications we're focused on, there are three primary buckets of IRDs. The bestrophinopathies, Leber's congenital amaurosis, and retinitis pigmentosa. We have chosen these programs specifically since they have common approaches that we can leverage, including cell biology, delivery method, and clinical trial design. We can differentiate as needed for each disease.
For example, LCA mutations are typically earlier onset conditions in children, and they are also more macular focused. While the retinitis pigmentosa mutations have a more concentric loss of peripheral vision. All of these programs are fairly straightforward subretinal IRD gene therapy programs, and one of the reasons we picked these indications is because we can potentially see a rapid proof of concept in clinic. We will go through much of this today as we look towards several clinical trial initiations and data readout in the next 12-18 months. We really are building a differentiated gene therapy pipeline. Our company is essentially built as a platform to develop these gene therapies and advance them in a very capital-efficient and time-efficient manner. For LCA5, we are currently enrolling participants in the run-in portion of our phase III clinical program.
This program has received multiple regulatory designations, including the Regenerative Medicine Advanced Therapy, or RMAT, and most recently, we were accepted into the new Rare Disease Evidence Principles, or RDEP program, focused on ultra-rare diseases. For BEST1, Dr. Mark Pennesi presented our data on the sentinel patient at the Macula Society in February, and we look forward to presenting our first full cohort of data in September. Our key focus today is to provide you with the disease profile and scientific rationale for our next three programs, RHO, RDH12, and MERTK, that are all progressing into the clinic. Here on slide 10, we've laid out our planned timelines. Importantly, current cash runway into 2029 will support five clinical development programs through multiple inflection points. We are really entering a pivotal time for the company.
Based on early success we've had with LCA5 and BEST1, and our recent fundraising activities, we are now in a position to accelerate our RDH12, MERTK, and RHO into clinic. This increases our total addressable market in a significant way and gives us multiple shots on goal. We're now funded to achieve readouts in our BEST1 and LCA5 programs, and also generate clinical data from these additional programs coming online. Currently, we expect as many as four clinical trial readouts in 2027. It is important to note that all of our programs treat various forms of rare pediatric diseases with the potential to receive priority review vouchers if approved. It's my honor to introduce our first guest speaker, Dr. Jean Bennett.
She is the inventor of LUXTURNA, which is the first gene therapy approved in the U.S. to treat inherited retinal diseases. She is one of the scientific co-founders of Opus Genetics, and remains a key member of our board of directors. Today, Dr. Bennett will provide an overview of IRD drug development and discuss the concept of structure function dissociation that underlies all of our programs.
Thank you so much, George. It's my pleasure to be here. I thought to set the stage for the next set of talks, I'd give you a little bit of background about the rationale for selecting the various targets that we've selected. Obviously, the optimal targets have to target the affected cells before they've degenerated, otherwise you can't treat them. Ideally, lack of function disease is optimal, since one can then reactivate the function and rescue the disease. We want transgene cassettes that will fit within the small cargo capacity of the adeno-associated virus, or AAV, and that AAV must transduce the target cells efficiently. The disease has to be severe enough to be able to detect improvement, and ideally in a fairly rapid timeframe so that we can see this improvement quickly.
We need the relevant animal or cell models to be able to develop proof of concept to be able to go forward. Ideally select diseases which are relatively prevalent so we can find enough patients to be enrolled in the clinical trials. The more challenging diseases are those that are developmental conditions, for example, those that begin the whole degenerative process in utero. Those would be very difficult to treat. There are also some technical challenges with large genes, fitting them into the small cargo capacity of the AAV. Ideally, we want disease that progresses fairly quickly because we don't want the trials to have to take 10 years or longer. It's more challenging if we don't know much about the natural history of the disease or if there's asymmetric disease, or if it's extraordinarily rare.
Shown in this graph is a diagram of the numbers of genes which, when mutated, cause retinal degeneration. Over time, the first ones were identified in around 1990. choroideremia and rhodopsin were some of the earliest. As you can see now, the number has expanded to more than 348 identified genes, and that's in large part thanks to the Human Genome Project. When we first started, and others first started considering gene therapy, gene augmentation therapy, the only two genes that were known were rhodopsin and choroideremia. RPE65, or retinal pigment epithelium 65 kilodalton protein encoding gene, were some of the earliest ones identified, and those have been targets of clinical trials. choroideremia and RPE65 were targets of Spark Therapeutics, and other people, including those that you'll hear later today, have been involved in trials for choroideremia.
Shown here are additional diseases which have been identified over the course of this progress in gene identification, and these are targets that Opus has selected that fit the characteristics that are listed in this slide in terms of optimal targets. In the next slide, obviously, if the retinal structure is relatively preserved, even though visual function is already impaired, it becomes possible to deliver the gene to rescue the function in a therapeutic window when the cells are still viable enough to be able to function. If one can pick the right patients and choose the meaningful endpoints for clinical trials, one can potentially demonstrate benefit, and that's exactly what has happened with LUXTURNA, which was the reagent that was developed to treat RPE65 deficiency.
In the next slide I'd like to show you two of the targets that Opus has initiated studies on. One is, they're both forms of Leber's congenital amaurosis. This is a severe early onset form of retinal degeneration, one of the most severe forms of retinal degeneration because it affects children and infants. LCA5 and RDH12 are both diseases which are first manifest in photoreceptor cells, unlike RPE65, which is the gene target of LUXTURNA. These are both ciliopathies. They're very rare. By imaging, we know that there are photoreceptors that are still available and treatable in childhood and young adults. So that satisfies one of the requirements. There are animal and cell models that can be used to demonstrate proof of concept.
However, compared to RPE65, these are more severe and earlier onset. So we hypothesized that by treating children, we could actually intervene well with the disease and potentially even prevent the disease. Shown to the right are some of the children who were the first to be identified with these diseases. The top one is one with LCA5, and underneath are RDH12 children when they came to visit my laboratory. In the next slide, one of the reasons why these two diseases are so dear to my heart is because of the patient and family partnerships that have been made over decades. Starting with LCA5, a Leber's congenital amaurosis conference was held in 1998 that was developed and formulated by parents of a child with LCA.
At that point, they didn't know what the cause of his disease was, they fueled the efforts of academics and really an international consortium to try to figure out what was the cause of this and other forms of LCA. Their child's gene was identified in 1997. Well, this child was born in 1997, but after this conference, his gene was identified some 10 years later in 2007. That picture on the lower left shows the team at Nijmegen in the Netherlands who had discovered this gene. That fueled a consortium to try to develop a treatment for this particular disease. The family continued to fund projects, including generation of a mouse model of this disease, which was made at Jackson Labs by Patsy Nishina, sent to my lab.
Together we all developed a reagent which we showed could actually ameliorate the disease in this mouse model. In our lab, we set up a GMP facility to generate AAV. Then we were lucky enough to partner with Opus Genetics and develop a clinical trial. Shown on the lower right is the team that delivered the first gene therapy for LCA5 in 2023. In the next slide, I'd just like to close by telling you what I think the status of retinal gene therapy is. There's abundant safety data. There are more than 140 different retinal gene therapy clinical trials that have been initiated. There are gene therapy centers around the world. Thousands of eyes have been injected. We have a lot of safety data.
There are numerous disease targets that have been tested and are in the process of being tested in the clinic with a variety of strategies, excellent safety data. Now there's familiarity with gene therapy surgical techniques, vector handling and storage, genotype/phenotype correlations, development of outcome measures all over the world. It's a very exciting time. There are more than half a dozen retinal gene therapy clinical trials which will read out within the next year, hopefully giving us additional approved gene therapy products besides LUXTURNA. Now, where are we with LUXTURNA, also known as voretigene neparvovec-rzyl? This is the treatment for RPE65, which is now approved not only in the United States and the European Union, but in numerous countries and continents around the world.
There is a great deal of long-term durability data that stems from the clinical trial that was run to approve this drug. It's more than nine years and counting of this durability data. The real-world efficacy is very similar to that reported in clinical trials. We're really optimistic that Opus is going to contribute further to development of treatments for these currently untreatable conditions. I'd like to hand off the next session. Actually, let me give this slide. There are numerous obstacles to retinal gene therapy that have been overcome, just as continuation of where we are. In the 2000s when we began with LUXTURNA, there was no path, there were no regulatory guidelines. Everything had to be de-risked, including the safety of subretinal delivery of AAV and dosing of AAV.
There was a lack of genotype patients because there was no reason to genotype them. There was no treatment, no clinical trials in progress. No one had enrolled pediatric subjects for gene therapy clinical trials. We didn't know the status of immune response, whether this would cause rejection or inflammation. We had no guidelines from the FDA, including whether or not it was going to be necessary to inject the second eye, the contralateral eye, what we needed in terms of control groups, et cetera. There was no natural history data and no relevant outcome measures, certainly no potency assays with which to measure the quality of the product. In 2007, when we began our first retinal gene therapy clinical trial, there was only one approved outcome measure, and that was reading the eye chart.
Now there are numerous potential outcome measures, including the outcome measure that was developed during the process of testing LUXTURNA. That's the multi-luminance mobility test. There are now virtual reality tests, there's perimetry, there are anatomical features, and also changes in disease progression. It's a very bright future for retinal gene therapy. Now I'd like to turn t he table over to Dr. Fan, who will tell you about RDH12. Thank you very much.
Thanks, Dr. Bennett. That was such a great overview of how far we've come with gene therapy and IRDs. Of course, you being so pivotal to all of that. Let's get into the slides. In the interest of time, I'm just going to start reviewing this disease, RDH12, which is truly one of the most devastating forms of early onset retinal dystrophies or degenerations that I see in my clinic. RDH12 is interesting because it draws a lot of parallels to the severity and intensity of vision loss to RPE65. We know RDH12 accounts for up to 10% of all LCA cases. That makes the global prevalence over 30,000, with a high concentration in the Middle East and North Africa. There are still quite a few patients in the U.S., probably underestimating it at about 2,500 patients.
Surely, as we know about all IRDs, the true prevalence is probably a little bit higher. These are images of a patient I see in my clinic, a young patient. As you can see on the images on the right, that you have essentially severe peripheral retinal atrophy. What's unique about this retinal degeneration as opposed to a disease like retinitis pigmentosa, is that you have more macular atrophy, which is central involvement early on in life. What you often see in these patients is they'll present in childhood with a diagnosis of retinitis pigmentosa, you kind of watch them progress very quickly into losing central vision in addition to peripheral vision, and that can be truly devastating for this patient population. Let's go to the next slide.
Not to bore you with the scientific mechanism of action of RDH12, essentially, as Dr. Bennett was saying, this enzyme and this gene has its function in the photoreceptors as opposed to the retinal pigmented epithelium. You can see that the job of the photoreceptors, the outer segments, is to process light and clear toxic byproducts like all-trans-retinal, which then can be recycled into the visual cycle. If you're unable to clear those byproducts, what happens is that the byproducts will build up, they'll dimerize, they'll create oxidative stress and damage to the photoreceptors in forms of entities like A2E, lipofuscin, that kind of thing. We know in RDH12, this process is very severe and will damage photoreceptors if left unchecked, leading to early vision loss in a disease that we call Leber's congenital amaurosis, or LCA.
Let's go to next slide. The ways that it is similar is that it has profound vision loss early on in life. We know that maybe in your teens or childhood, you're about 20/200, but it can steeply decline very quickly thereafter, hitting counting fingers or even hand motions or light perception in your 30s and 40s. Which is truly devastating and much more severe than a lot of other inherited retinal diseases. Drawing your attention to the diagram on the right, you can see that the OCT image of the patient of RDH12 has more disorganized anatomical layers of the retina as compared to the image of the OCT of RPE65.
However, we have found on electrophysiology that there is better cone-mediated sensitivity in patients with RDH12 despite the anatomical disorganization of layers as compared to RPE65, which may suggest because the pathobiology is relatively similar, that perhaps these cones are rescuable because they still maintain pretty good sensitivity despite what we see on exam and also on imaging to be more severe retinal disorganization or potentially retinal atrophy. There is a therapeutic window here for us to produce a therapy that may mimic that of LUXTURNA, that may be able to treat patients similar in some ways to RPE65, and maybe optimistically be able to rescue in maybe a more efficient way or better way, this cone-mediated sensitivity before it causes damage to the central vision.
I'm going to pass it over to Ash now so he can review the scientific overview. Ash is the Chief Scientific Officer of Opus. Thanks.
Thanks, Dr. Fan. OPGx-RDH12 is an AAV8 vector designed for one-time subretinal administration to deliver functional copies of the RDH12 enzyme to photoreceptors in order to restore visual function using a photoreceptor-specific promoter. In our studies, a mouse model of RDH12 deficiency was used to test OPGx-RDH12 to test for expression as well as function of RDH12 in the mouse retina. We demonstrated with Dr. Bennett that OPGx-RDH12 AAV restores RDH12 enzyme expression in the mouse retina, as shown on the right panel, and in a dose-dependent manner, also restores enzymatic activity and function approaching that of wild type mouse retina levels. The RDH12 deficient, or as we call it, a knockout mouse model, is also highly susceptible to light damage, likely to acceleration of phototoxic stress and subsequent photoreceptor apoptosis.
Left untreated, these RDH12 knockout mice treated with high intensity light exposure to the retina degenerate, as shown by thinning outer nuclear layers where the photoreceptor nuclei reside, and you can see that on the top panel. However, AAV8 encoding for RDH12 expression in this published study was capable of preventing this retinal degeneration. Furthermore, mouse behavioral testing used to assess visual function also improved with AAV gene therapy for RDH12, as shown on the bottom half of the panel. We therefore are well poised to now investigate OPGx-RDH12 safety and efficacy in clinical studies. With that, I would now like to turn the call over to Professor Robert MacLaren to discuss MERTK IRDs.
Thanks very much, Ash, and also thank you to Jean for a very helpful summary of the history of the retinal gene therapy, which I've been following myself for over 20 years now. I'm Robert MacLaren, I'm a professor of ophthalmology in Oxford, and I've been involved in gene therapy trials for a number of conditions, choroideremia, X-linked retinitis pigmentosa, which take up a lot of my time at the moment, and also the work we've been doing with age-related macular degeneration. MERTK is one of those inherited retinal diseases that can be very severe in early onset and cause what we refer to as Leber congenital amaurosis, in other words, very poor vision from birth.
More often, what we see is missense changes where patients have a disease that is clearly causing them visual impairment, but still with some ability to see things and read the chart. This particular condition is caused by a mutation in the gene that encodes a protein that is involved with the phagocytosis of photoreceptor discs. Most significantly, the MERTK gene is expressed in the retinal pigment epithelium. We know this cell in particular is readily transducible with low levels of AAV compared to photoreceptor transduction, again, which helps us in terms of predicting the clinical trial outcomes in terms of safety. The prevalence worldwide, I have patients in my clinic in Oxford, but it's particularly high in the Middle East.
My colleague, Fowzan Alkuraya, originally did a MERTK gene therapy trial at King Khaled Eye Specialist Hospital in Riyadh. The reason for that was that it was funded by a family, the Al-Radi family, who unfortunately have MERTK in the family, and was really done almost like as an off-label treatment. I was very much hoping that Fowzan would continue the program. In fact, I invited him to Oxford to come and speak about the results of the trial, it sort of faded away, unfortunately, at that stage. We do have some very good examples from that paper that he published on the safety, and in some cases, efficacy of the treatment administered to a small cohort of six patients. The phenotype, very similar to all of these inherited retinal diseases.
If you look at the picture at the bottom right, kindly provided by Ken. Ken, I'm going to comment on your image. I hope you don't mind. There is some debate about whether we can see subretinal clumps in the subretinal space. You can see in the bottom right the retina, the subretinal space. There is certainly good data from the animal models that these are photoreceptor outer segments that are sort of clumped there. It's one of those things that we look for potentially as a phenotype to identify patients and try and narrow down the genetic testing. The ability to phagocytose the outer segments is all part of the visual cycle indirectly. Not surprisingly, these patients have night vision loss, peripheral vision loss.
Indeed, the actual clinical features are very similar to those seen in many of the other inherited retinal diseases. If we could go to the next slide, please. This just shows a little bit more about the mechanism. You can see that the MERTK receptor is on the surface of the retinal pigment epithelium. We can translate a lot from the LUXTURNA program, which is also targeting retinal pigment epithelium, to MERTK. What we might expect to see, as indeed we have seen with other inherited retinal diseases, is when you put back a protein that has a critical role in maintaining the structure of the photoreceptor, particularly the outer segment, then you can expect to see an improvement in the outer segment structure. We've seen that with OCT scans as well.
If you improve the outer segment structure by whatever means, you can also expect to improve the retinal sensitivity, which is very important because that gives you a functional endpoint Functional endpoints are much easier to achieve with a small number of patients than anatomical endpoints, in which one would have to wait quite a long time to see a difference in slowing of degeneration in a treated eyes compared to untreated eyes. We know that the function endpoints are well established. It's going to be low luminance visual acuity, best-corrected visual acuity, microperimetry. These are the tests we do all the time on our patients, and they're all recognized as being useful tests by the regulators for clinical trial approval. Ideally, we'd like to see something within one year improvements, which would justify approval of the treatment.
The failure of the MERTK results in accumulation of this outer segment debris in the subretinal space, and there is undoubtedly a window where the function is impaired, but the cells are still there, potentially could be reversed with a clinical trial outcome measure seen very quickly after gene therapy. Indeed, that is seen in the animal models. Next slide, please. Again, this just explains a little bit about what I've said, the functional loss. Okay. Any disease in which there's a loss of function before you get degeneration has a potential opportunity for reversal of functional loss by gene therapy, which gives us a nice clinical trial outcome measure. The reduction in vision, as I said, most cases we see it in childhood, teenage years.
Most patients manage reasonably well, but they do lose vision. We do have a large cohort of patients who are treatable. These patients will, in general, have had relatively normal development. They may have problems in childhood with night vision, but they will be able to use the visual system, and it gives us an opportunity, a relatively large window in their lifespan, where we could perform the intervention. As I said, because primarily of the preserved structure as well. The phenotype on the right-hand side, again, to be honest with you, it's very, very similar to all retinal degenerations. What you have to look at, if you are familiar with the structures of the OCT scan, is the bottom scan.
You can see the black line, which is basically the outer nuclear layer in contact with the reflective line, which is the retinal pigment epithelium. This outer nuclear layer is relatively well preserved. In other words, the photoreceptors are still there. They're probably largely non-functional because the outer segments cannot grow. They're not being properly phagocytosed. There's debris in the subretinal space. The cells are there. When the cells are there's a capability of regeneration following gene therapy. By the way, the reference we've got at the bottom there is the Gargi reference, which is the clinical trial led by Faisal Alkherif, who's a geneticist, when he was working in Saudi Arabia. I think, let's check. That's pretty much all from me.
I'll be hanging around for questions afterwards, and I'll gladly hand over to Ash to go through the molecular biology of the treatment. Thank you.
Thank you, Dr. MacLaren. Our clinical candidate, OPGx-MERTK, is an AAV2 vector designed also for one-time subretinal administration to deliver MERTK gene within RPE cells, and in this case it uses an RPE specific promoter. The capsid used, AAV2, is the same as that used in the approved product voretigene neparvovec or LUXTURNA, which as Dr. Bennett eloquently described, has now had a long track record of improving clinical outcomes in patients with RPE65 associated IRDs. The MERTK deficient mouse model, which has been published and established for some time now, allows us to study the efficacy of MERTK gene therapies in a relevant context. This mouse model rapidly loses photoreceptors and concurrently loses visual function. This decline can be prevented through subretinal injection of AAV encoding for MERTK.
Specifically here, gene therapy treated mice exhibited improved outer nuclear layer thickness, as shown on the top right panel, and improved electroretinogram or ERG functional responses, as shown on the bottom right panel. Furthermore, using another model, this case a rat model of MERTK deficiency called the RCS or Royal College of Surgeons rat model of retinal degeneration, we demonstrated that the clinical candidate, OPGx-MERTK, was capable of dose dependently reducing photoreceptor degeneration in this model when compared to a control injection, which had no therapeutic response, as outlined by the blue dashed line on measures of outer nuclear layer thickness. With that, we look forward to investigating the safety and preliminary efficacy of OPGx-MERTK in clinical studies.
With that, I would now like to turn the call over to Dr. Lejla Vajzovic to discuss ADRP RHO IRDs.
Thank you. Thank you very much, Ash. Good morning to you all. It's truly a pleasure to be here with all of you. It's really a pleasure to be included with such a outstanding, really world-renowned experts and clinicians, scientists, and industry leaders. It's super exciting to be here because the future of, I think, care of IRD patients is looking really bright, and I commend the Opus Genetics team for working so hard to provide more options for our patients in the future. As mentioned, my name is Lejla Vajzovic. I'm professor of Ophthalmology, Pediatrics, and Biomedical Engineering with tenure at Duke University.
As a clinician and surgeon who has been taking care of pediatric and adult retinal patients with IRDs, and who has been delivering the gene therapy surgeries for the last 15 years at Duke, I'd like to provide some more perspective on RHO, specifically associated retinitis pigmentosa, what I see in my clinic, how these patients progress over time, and what's really the essence of the disease, and why this may be a great therapeutic approach to treating these patients. Let's dive into RHO-associated retinitis pigmentosa, and one of the most common inherited retinal degeneration that we encounter in our practice. There's been more than 290 disease-causing mutations that have been identified. RHO variations account for approximately 20%-30% of autosomal dominant retinitis pigmentosa cases that we see. Importantly, this is not an ultra-rare disease.
Currently, estimates suggest approximately 8,800 affected individuals in the U.S., and more than 30,000 across the global markets. From a clinical perspective, these patients often first present with night blindness and difficulties in dim environment. This is really the first complaint we will hear very much from our patients. Over time, they experience progressive peripheral vision loss while maintaining the useful central vision for years to come. I think this combination of meaningful patient population, prolonged disease course, I think makes RHO an especially attractive target for therapeutic delivery. Next slide, please. Let's dive into biology itself. One of the aspects that makes RHO particularly compelling is that we understand the disease biology exceptionally well. RHO encodes rhodopsin, the critical photopigment with the rod photoreceptors that really enables vision in a low light conditions.
When mutation does occur, the resulting protein can misfold or function abnormally, triggering cellular stress and progressive photoreceptor degeneration. Importantly, many dominant RHO mutations act through toxic gain of function or dominant negative mechanism. As a result, these therapeutic approaches most addres s the mutant protein itself rather than really adding another copy of the gene. We really want to address that mutant protein than just kind of multiplying and adding new copies. Deep understanding of disease biology really provides us with stronger scientific rationale for targeting gene therapy approaches for certain. Next slide, please. One of the most encouraging aspects of RHO-associated disease, it's often relatively slow progression. This disease typically begins with rod dysfunction during the childhood. As I mentioned earlier, it presents with night blindness and peripheral visual field constriction over time.
The cone, the central vision degeneration, is typically the last one to occur in this disease course. We do understand that there are 2 classes, two broad phenotypes that have been described here. Class A patient experiences more of a severe disease with early functional loss, while Class B patients often maintain rod function and preserve retinal structure well into the adulthood. This distinction is important because many patients, again, retain viable photoreceptors for years, creating meaningful opportunities for us to intervene therapeutically and hopefully stop their deterioration or at least slow it down. The structural and functional data shows that there is definitely room for intervention.
The disease progression can very much, as mentioned earlier, in other disease, it can be measured as such with imaging and functional testing, providing us now tools to really understand and how to develop clinical trial designs, follow the patients, and ultimately report on outcomes. Before I transition it back to Ash, I just want to summarize. I believe RHO represents one of the most compelling opportunities in Inherited Retinal Diseases because it truly combines three key characteristics for me. First, we have well-understood disease mechanism. Second, meaningful and identifiable patient population that we can treat. Third, we have a therapeutic window where the photoreceptors remain present and potentially are amenable to interventions. Those characteristics, make RHO an attractive target for gene therapy, especially in development.
With that, I'm going to turn it back to Ash to discuss really their Opus RHO program. Thank you so much.
Thank you, Dr. Vajzovic. In this case, we're talking about the clinical candidate OPGx-RHO. This is an AAV5 vector. Like the others, it's for one-time subretinal administration for patients with autosomal dominant retinitis pigmentosa associated with RHO mutations. OPGx-RHO is a mutation-independent single AAV construct for silence and replacement. This is designed to replace mutated rhodopsin proteins with a functional non-toxic copy. The vect or targets rod photoreceptors using selective promoter technology. We've been fortunate to have demonstrated preclinical safety and efficacy in two large animal models of ADRP RHO, as previously reported. Here in the canine model, in collaboration with Dr. William Beltran of the University of Pennsylvania, we have tested safety and efficacy of the clinical candidate in this model of ADRP RHO mutations.
The canine model is an English mastiff with a naturally occurring point mutation in RHO, and expresses nearly equal amounts of wild type and mutated RHO proteins, and captures well, we think, the structural degeneration observed in Class B human ADRP patients, as you see on the top right. Within the first two years of life in this model, there is a substantial loss of photoreceptors. However, this time course can be accelerated even further with light exposure to enable the study of therapeutic interventions within an efficient window. In fact, with a one-minute light exposure protocol, rapid photoreceptor loss down to even a single RHO of outer nuclear layer nuclei can be observed as early as two weeks post light exposure in the ADRP RHO, but not the wild-type canines.
Y ou can see that on the bottom right panel. This accelerated degeneration model has been useful for us to test our clinical candidate. Here on the left panel, we can see that the retina's post-injection of subretinal AAV and light exposure treatment have exhibited significant outer nuclear layer retention in the treated areas. The dashed lines are actually demarcating the subretinal bled boundaries here. Immunofluorescence on the right panel shows rhodopsin and cone staining with cone arrestin in green and red respectively. That histology and immunofluorescence confirms our observations in vivo. What we're seeing here is photoreceptor cell body retention with observation of rod outer segments as well, which was only observed in the subretinally treated areas, not the proximal untreated areas.
In the addition to the canine model, we have also tested on the next slide, OPGx-RHO safety and efficacy, in this case, in a humanized swine model of ADRP RHO. This was in collaboration with Dr. Maureen McCall of the University of Louisville. This model exhibits a human P23H RHO variant, which is highly prevalent in North America. The retina in this model rapidly degenerates by postnatal day 60, such as there is only residual rod structure and function, followed by subsequent cone degeneration. Thus, this also, we believe, accurately models the structural and functional degenerative time course that we see in ADRP RHO patients. We observe that OPGx-RHO here, as shown on the right, preserves rod photoreceptor structure and reduces the aforementioned degeneration.
Specifically, if you look in the untreated panel on the bottom left, untreated rods are sparse. They are dysmorphic, and rhodopsin is mislocalized in these retinas. However, when we treat with OPGx-RHO, we see that it's capable of dose-dependent preservation of rods, as shown in the upper right panels. In this case, you're starting to see proper localization of rhodopsin and preserved cell morphology. Not shown here, but also previously presented, was preservation of the rod-isolated full-field ERG in treated animals, but not untreated animals. We also have observed preservation of cone structure throughout the study, as shown on the upper right panels. This is also correlated with preserved cone ERGs, again, not shown here, but previously presented. With that, we look forward to investigation of OPGx-RHO in clinical studies.
On that topic, I will turn the call over to Dr. Sally Tucker, our Chief Medical Officer.
Thanks so much, Ash. Good morning, everybody. As Ash said, I'm Sally Tucker, Chief Medical Officer. We go to the next slide. As mentioned earlier, when we consider the IRDs we're targeting, they fall into three separate buckets. We have the bestrophinopathies, which includes both ARB and BVMD. These patients with ARB, it generally occurs much earlier on than BVMD. The progression can be slow and often variable. It results in a defective calcium-activated chloride channel that patients often complain of metamorphopsia, decreased central vision, and photophobia. In the other two buckets, we have LCA and retinitis pigm entosa. LCA, which we have touched upon already, generally occurs from a much earlier onset. Patients are born with the LCA, and it affects vision much earlier on.
In many cases from one to two years, with many patients being blind early on. Whereas in retinitis pigmentosa, the vision loss can occur in the adolescence to adulthood, so there can be progression over years. However, regardless, with these patients, they have abnormal rod-cone functionality, decreased central vision, night blindness, visual fie ld loss that results in tunnel vision, and for many patients, nystagmus. As we indicated previously, our goal is to reinstate the functionality of the retina in those patients that have structure so that we can then see vision improvements in a relatively short time period. We go to the next slide. This indicates the signs and symptoms of the various IRDs that we're targeting.
What you can see here is that the signs and symptoms really key into the development and design of the protocols for all of our IRD programs, with us addressing either structural endpoints or key functional endpoints. You can see here with many of the signs, we're really focusing in on fundus photography, fundus autofluorescence, and SD-OCT. As Dr. MacLaren indicated, it can be that these changes occur over a longer time period. However, with the symptoms, we're focusing in on best corrected visual acuity, low luminance visual acuity, FST, microperimetry, contrast sensitivity, virtual reality, MLMT, perimetry, static perimetry, and kinetic visual field testing. In addition, we also can look at pupillometry and quality-of-life parameters as well, which are important to consider in those symptoms that might be more hard to quantitatively assess.
Our clinical designs follow a data-driven dose exploration approach. What does that mean? Well, with any phase I/II study, the primary purpose is to determine safety. We want to ensure that the drug delivery is safe and is well accepted by the patients that it is administered to. We're also wanting to see efficacy, and we're wanting to see as maximal efficacy as possible. What we will do is we take a data-driven approach. We utilize an independent data monitoring committee, and we will present the data to the committee. We're looking for safety. If there is some efficacy there, but it doesn't represent a maximal approach, then we will dose escalate into higher doses.
However, if there is evidence to suggest that a maximal efficacy signal has been reached, we would then progress into a pivotal trial without any further dose escalation. We go to the next slide. We have three programs that we are entering the clinic over the next 12 months, it's an incredibly exciting time. We're expecting RDH12 to be initiated later this year, MERTK in Abu Dhabi in the first quarter of 2027, RHO utilizing global locations in the second half of 2027. We go to the next slide. We do have a number of strategic partnerships, one of which is with the RDH12 Alliance. This encompasses the Fund for Sight in the U.S. and Eyes on the Future in the U.K. I see the RDH12 is a co-developer in our RDH12 program.
We have received funding from the alliance to support the progression of this clinical trial. We have regular calls to discuss the trial design, providing updates to the patient community. We are actually at their family day, the RDH12 Family Day, that's being held in London this weekend, where we'll be providing updates of our current RDH12 program. In addition, we have a partnership with the Department of Health – Abu Dhabi. As indicated earlier on, MERTK has a higher prevalence in the UAE and Middle East. We have received funding to support the execution of the clinical trial there.
We also have other partnerships with Hope in Focus, Foundation Fighting Blindness, and other organizations that really help to elevate awareness of the clinical development programs we're running, support our patient enrollments, and optimize recruitment to the studies that we run. Moving on to patient recruitment and retention strategies, which are key in the overall success of any clinical development program. It's true that globally, more than 80% of clinical trials fail to enroll in time. How can we overcome that? We're developing patient education videos. We want to increase awareness of the IRDs that we're focusing in on, but also help to provide more education to the patients that are considering participation. We're interviewing patients that have been involved in prior clinical trials. What were the questions that they had?
What were the thought process that they went through? How can we provide more material to the patients in a mentorship capacity to support the decision-making that they might have? Where possible, we'll initiate observational studies before moving to the interventional study, which will help to identify IRD patients in a proactive way. As I said previously, we optim ize patient engagement. Where possible, we'll work with patient alliance groups, such as the RDH12 group, be involved in family days. We also have a newsletter that patients can sign up to through our website. We also reach out across patient databases, utilizing many of the databases from Foundation Fighting Blindness, Sano Genetics, Invitae, and others. The other thing that we need to consider is that there is an 88% clinical trial dropout rate in longstanding studies.
With our studies, they have a five-year follow-up. It's important to collaborate and consult with patient advisory boards, getting their input to our protocol design, making sure that we're selecting the right endpoints, also making sure that we're considering the burden on the patients being involved in the study. Finally, what we are also piloting as part of a way to improve retention in our clinical trials that goes above and beyond the traditional stipend that you see in U.S.-based trials, is that we also want to give something back to the patients. Making sure that we continually educate them throughout the course of the trial, reminding them why they're in the trial, and what we're hoping to achieve through the trial.
Also providing a coaching initiative to these patients so that they're getting something back in return for their time, which is not insignificant over a five-year period. Lastly, we're all about increasing the patient's voice. This is one of our patients that was recruited to LCA5 and was actually featured on Good Morning America. We're not only wanting to increase awareness amongst the IRD community, but more broad than that. What does it mean to a pati ent living with blindness, the impact that it has on them, and the impact that being in a trial can have on them, and the treatment and what it means to them? We're very proud of this initiative and how we've supported Lindsey in increasing awareness of LCA5 in this way.
I'm now going to hand over to our President, Ben Yerxa.
Thank you, Sally. To everyone out there, as a reminder, you can submit a question using the Ask a Question button at the top right corner of the screen. We've had a few that have come in. Let me sort through these real quick. For the first question, for our guests, we should probably consider this sort of like a lightning round because we've got a number of questions. I think for Doctors Fan, MacLaren, and Vajzovic, let me read this out loud. For IRDs that aff ect a relatively small number of patients, such as LCA5, RDH12, and MERTK, how difficult is patient identification? Are there ongoing efforts to increase patient genetic testing? How motivated are patients to undergo such testing when no treatments are available yet?
I can briefly take some of those questions. I would say, obviously, they're very rare diseases. Patient identification for an IRD specialist typically comes naturally. You get a lot of referrals, not just from the retina community, but also the optometric community and fellow ophthalmologists, general ophthalmologists. Typically, if you're in a referral center, they do come, and oftentimes you can see multiple rare diseases of the same gene mutation in the same day. I think a lot of patients are incredibly motivated despite the fact that there may not be an approved therapy, just because there's other implications beyond just clinical trial and FDA-approved treatment, including family planning, protecting future generations, genetic counseling. All those things are major factors, and perhaps sometimes the primary motivation for genetic testing.
With efforts from Opus and collaborations with FFB, there's been increased availability, at least in the U.S., to get low-cost genetic testing universally for all patients. I've had no issues testing these patients, and almost 100% of them will do it because they're motivated for sure.
Great. Thank you. Dr. MacLaren?
Yeah, in the U.K., and I think in Europe as well, virtually everyone will have genetic testing. It's an essential part of the workup of any patient with an inherited retinal degeneration. Indeed, if anything, the electrophysiology is what's gone out the window. We tend not to do that very much anymore because we can tell very well from the imaging how advanced a patient is and monitor progression. I think it's important to think about this more globally, okay? I agree that there are individual genes here which are very rare, the strategy is the same. It involves measurements of OCT, measurements of visual function. It involves an AAV vector. We know now exactly what the dose is. There'll be differences in the refinements of different vector. The shipping, manufacturing.
Don't forget, manufacturing is a key part of regulatory approval that should not be underestimated. In my view, sometimes the manufacturing is more complicated than the actual clinical trial. You've got the administration, the surgery, the subretinal injection, all the technology that's developed quite a lot, followed by the monitoring, the checking for inflammation, and all the rest of it. If you lo ok at all the diseases together, it becomes quite common. We're talking about young people as well. Always say, since we've been better at managing diabetic retinopathy, the inherited retinal diseases collectively are now probably in the U.K., the most common cause of untreatable sight loss in people of working age. If that's not an unmet need, where is it?
I think what we've got quite nicely here is like a platform technology that overlaps on many different genes and therefore has many more patients than it'd be just for one single gene disorder.
Very well put, and I agree. CMC is half the battle here in gene therapy. Dr. Vajzovic?
Just to add to those amazing answers really from Dr. Fan and Dr. MacLaren, I would say in the U.S., everybody that steps into retinal clinic that has any hint of IRD will get genetically tested. I think that has been really the crucial change for all of us in taking care of these patients. Not only will the patient is helped, but really we're discussing the effects of entire family. I feel like as a result due to genetic testing, now we're diagnosing siblings and other family members e arlier than we might have done before. That has been really the big change. Lastly, we have amazing technology to image these patients in clinic these days.
Completely agree that we're relying on imaging more than ever to help us understand disease and in clinical trials to help us understand responses.
Great. Thank you. Next question I think I'll direct to Dr. Sally Tucker. This one goes, "In general, are you planning on testi ng these next three gene therapies in children or adolescents early on in clinical development, or will data updates in 2027 likely be in adults?
The clinical trials will be designed to incorporate the inclusion of both adults and adolescent patients. How they'll be structured, it's similar, if you remember the slide that I showed and the platform approach. It will include two adults, and then a minimum of three adolescent patients. We establish the safety first in the adults before moving on to the adolescent patients. Although the adolescents will be recruited to the study later on, the plan is to include younger patients in this first in-human study.
Great, thank you. A question I think I'll direct to Dr. MacLaren. How much do you think the data from the ex-U.S. trial in ME RTK will help the eventual development in the U.S., U.K., and Europe?
Well, it wasn't really done as a proper clinical trial in terms of particularly having a natural history beforehand, which you'd normally have a year just getting baseline data to know how accurate the tests are. Then the patients were selected with some very end stage because they're part of a family. I think, there's limited data we can get across the cohort, but there was one patient who did particularly well with vision, and these patients have not had any major side effects. The effects we've seen following the gene therapy with MERTK are very similar to that seen elsewhere. I think if I were writing the investigator brochure or preparing the work for the regulators, I'd certainly be citing this trial as a good exa mple of having used the vector before in humans.
I think that would make the process a bit smoother and probably even less requirement for doing NHP work in order to gain regulatory approval.
Great point. Thank you. A question now for Dr. Bennett. For RDH12, could you expand on the similarities and differences from RPE65, especially on the preserved cone sensitivity? Could you talk about the therapeutic window for RDH12? Is there an optimal treatment age, early childhood versus adolescence? Finally, it's a long question, on the preclinical RDH12 data, any insights on how much restoration of enzyme expression is required to achieve meaningful functional benefit?
Great questions. The bottom line is we don't know because we haven't run the trial yet. This disease is more severe than RPE65 deficiency. The symptoms are manifest earlier, and the degeneration is a little bit faster. There is a great natural history study that is being carried out, and has been carried out by Dr. Tomas Aleman and colle agues, which is giving us a lot of information about the optimal time points of treatment in terms of the rates of progression. Likely, I would predict we'd be able to rescue vision at least through adolescence. Probably the best outcomes are goin g to be in younger children. The other question was, can you re peat the second part of the question in terms of enzyme levels?
How much restoration of enzyme function, like % restoration of function you think will be relevant for improving?
Right. Knowing that heterozygotes have fairly normal vision, we believe that if we restore up to 50% of the level of enzyme activity, that should be sufficient. Even a small amount of enzyme activity should be helpful. Similarly to what we have found with RPE65 deficiency, there may be just a rate-limiting step which we need to overcome to be able to deliver some vision.
Got it. Thank you. The next question came in. We'll think about who wants to jump in to answer it. It is, how should we think about ranking potential pivotal endpoints for each program? Among the programs in development, do you see clusters of programs for which you expect the clinical development path or pivotal study designs to be the same in terms of endpoints, number of patients, length of trial, et cetera? I don't know who wants to jump in on that. Maybe, Sally, you want to start?
Sure. I think that it's a little early to determine what our pivotal trial endpoints, primary endpoints would be at this moment in time. I think that all of our assets are rare or ultra-rare. Therefore we're in this unique position to be abl e to get regulatory recognition such as RMAT, orphan designation, RDEP, which really allows close collaboration and discussions with the agency. That's certainly something that we embrace. I think that with these IRDs as well, there also needs to be consid eration of novel endpoints and utilizing novel endpo ints, also stat istical methodology as well to be able to determine mean net benefit. These are all things that we can consider when talking to the agency. I think that microperimetry is an endpoint that we're very interested in from determining central macular sensitivity.
I think it's a little early to say whether that would be uniformly utilized as our primary endpoint for all our pivotal trials.
All right. Thank you. All right, last question in the first part here. Across these defined IRDs, are certain mutations considered higher priority in terms of progression? Does this impact Opus' gene the rapy development prioritization? Might be back to you, Sally, unless one of the KOLs want to jump on that as well.
Can you repeat that, Ben? Sorry.
Yeah. Across all these IRDs that we're looking at, are certain mutations considered higher priority in term s of progression like LCA versus RP? Does this impact our prioritization of the pipeline?
I think the prioritization of our pipeline is much led by our manufacturing efforts and when we're ready to take the various assets into the clinic, rather than the prevalence or the severity of the disease. At the moment, as I said, we're expecting RDH12 to be in the clinic at the end of this year, with MERTK in the first quarter of 2027, and RHO in the s econd half of 2027 . We'll be bringing these as quickly to the clinic as we can, dependent upon when we have availability of the drug and can push these forward.
Great. Makes sense. Dr. Bennett, anything you want to add to that?
No, I would agree with what Sally said. We plan to move forward with all of these candidates in a regimented timeline. We move as quickly as possible. Of course, there may be some factors which would make one set of mu tations, one disease target move faster than another. At this point, we can't predict.
Great. Thank you. All right. Great session for part one. Thanks to everyone for your participation. Thank y ou to all the speakers and all the great questions that came in. We're now going to move to part two of our agenda. I would now like to turn the call over to Dr. Bart Leroy to begin our clinical program discussion with LCA5.
Thank you, Ben. Thank you to everyone for inviting me to be part of this beautiful series of presentations. My brief is to talk on the LCA5 update. Can I have the next slide, please? What is LCA5? It's actually an early-onset severe inherited retinal disease with early-onset visual loss, as so many we've discussed previously in the first part of the meeting. The LCA5 is a particularly severe disease with very early onset loss of vision. It supposedly represents about 2% of all LCA cases. That would be globally 3,200-plus patients. Within the U.S., about 170 approximately thought to be there. It's a pigmentary retinopathy, which is typified by macular atrophy quite early, but preservation of photoreceptors in the pericentral area of the macula.
The vision loss typically starts in infancy, and patients often have just vision of hand movements or light perception. Nystagmus and hyperopia are things that are not only seen in this condition, but certainly also here. All people with congenital bad disease or very early onset bad disease have nystagmus and hyperopia. The photor eceptor cell loss also leads to the fact that it's very hard to obtain any visual fields in such patients, although there is potential because there's preservation of the pericentral photoreceptors. Can I have the next slide, please? The Opus Genetics LCA5 gene therapy, which is currently being used and tested, is designed to restore a key protein of the visual cycle. Basically, that protein is called lebercilin.
It's actually a ciliary protein that is critical for the function of the photoreceptor outer segments, mostly because it works in the connecting cilium. All of the proteins that are involved in what is translation of light into electrical signals, the phototransduction, are being produced around the nucleus and then have to travel all the way to the outer segment to do the phototransduction. Lebercilin is very important in getting them there. The photoreceptors, as we said before, can actually survive quite long until the third decade of life, and that is suggestive again of, as so many of the diseases we've been talking about, of having a window of time during which treatment can happen.
OPGx-LCA5, an Opus Genetics LCA5, is designed to address the mutations in this gene, and it's clinically a de-risked AAV8 vector that delivers a functional copy of the LCA5 gene directly to the photoreceptor cells using similar promoter technology as was used in LUXTURNA. It's a single subretinal injection. Next slide, please. What is remarkable is that adults have been treated, what we're showing here is that the mean change from baseline and visual acuity i n the adult cohort with three patients involved is continuing to be significant, as you can see on the left-hand side with the orange line. An improvement is upwards in this slide. On the right-hand side, you see for the first time until month six, the results coming from the pediatric cohort, equally three patients.
You can certainly see that there's an improvement, a significant improvement in best-corrected visual acuity. Next slide, please. You can also continue to measure function. In this slide, for example, we talk about cone function as measured using the FST or full field stimulus test, actually full field sensitivity testing, that is showing on the left-hand side what we do with red light and with blue light in the adult cohort. On the right-hand side, you see the pediatric cohort. You can s ee a significant improvement again for both colors used in the cohorts, both adult and pediatric. The pediatric up to six months and 24 months for the adult cohort. Next slide. You can also test sensitivity if possible, that is if fixation is sufficient, using microperimetry.
In microperimetry, separate protocols are available. For here, for example, it's a 10-2 protocol that was used. This is a photopic test. As you can tell, the sensitivity in one patient, adult participant 0104 and pediatric participant 0106, the two only patients who were capable of doing this test, shows an absolutely significant increase in sensitivity in the central area of the macula, and actually a little bit of a movement of the fixation of the patient towards the foveal area. Both patients show significant increase in function of the central area of the macula that is consistent with the treatment effect. Next slide, please. One last thing that I just wanted to mention is what do people say? Patients actu ally report changes in their daily life.
Activities of daily living are significantly improved, and for example, in the adult participants, 0101 reported being able to identify her children within a larger group of children one month after the surgery, which she couldn't do before. Navigating urban environments independently and no longer requiring continuous use of a cane was reported by 0104. That's the adult patient who was able to do the microperimetry. If we go to the pediatric patients, for example, the 0106 patient, also the one with the better fixation so that she could do the microperimetry, reported a noticeable difference in the visual brightness between the treated and the untreated eyes. I said it was a girl.
It's actually a boy. I'm sorry. Able to watch basketball, important for children, I think, and can see the players and follow the ball instead of watching the score ticker and listening to the commentary . I think with that, I've shown that there is a real treatment effect of the Opus Genetics LCA5 program. With this, I'd love to pass on to Ash again.
Thank you, Dr. Bart Leroy. There are over 300 mutations associated with Best disease, which we will talk about now, there are several distinct phenotypes with both dominant and recessive modes of inheritance. The dominant forms include ADVRB, which is autosomal dominant vitreoretinochoroidopathy, then there is a highly prevalent phenotype which is called BVMD, or Best vitelliform macular dystrophy. It's named for the hallmark egg yolk or vitelliform macular lesion in this disease. Then there's the recessive form, autosomal recessive bestrophinopathy. Disease onset and severity of Best can vary. BEST1 is a calcium-activated chloride channel, or CaCC, and it is expressed in the retinal pigment epithelial cells, and it's responsible primarily for retinal ion and fluid homeostasis. It follows that dysfunction in the BEST1 channel and its activity can result in a number of vision-threatening complications that you see here.
As we discussed, there are several variants of BEST1. Looking a little bit closer, the recessive form, BEST ARB, lacks functional copies of BEST1 expression in the RPE. The more common dominant form of Best, which is associated with BVMD, for example, has two different forms. It's a loss-of-function and gain-of-function variant type. That's a critical distinction that we're making there, because it's thought that gain-of-function dominant mutations are unlikely to be treatable with conventional AAV gene augmentation, which is the focus of the Opus clinical trial with our candidate, OPGx-BEST1. However, we and others have demonstrated that loss-of-function mutations, in contrast, are treatable with AAV gene therapy, and those happen to account for the majority of BEST1 mutations, perhaps over 98%.
The genetic test in the clinic used to diagnose BEST1 IRDs may not report this detailed loss-of-function, gain-of-function information. Opus has developed a paradigm to help predict treatment responses to BEST1 gene therapy and help ensure that the patient carries indeed a loss-of-function mutation which is going to be amenable to gene therapy. We're in the process now of testing every known BEST1 mutation for treatment response using tools such as iPSC-derived RPE cells and other engineered mammalian cell models. In this case, we use techno logy such as patch-clamp electrophysiology and fluoresce nce reporter assays, which allow us to directly or indirectly measure the chloride conductance function of the CaCC channel. We've developed these in-house to understand first if the mutation is a loss-of-function or gain-of-function mutation, and also whether or not it is amenable to BEST1 gene correction.
When we receive the genetic test, we can look this mutation up in our test battery to see if this mutation has been tested for personalized responder, non-responder type analysis by Opus. We will be using this information in collaboration with our community of specialists to help select patients for clinical investigations of our candidate, OPGx-BEST1. This is a single AAV2 vector for one-time subretinal administration and also features an RPE-specific promoter. With that overview, I'm happy to hand the call over to George for a brief clinical review of BEST1.
Thank you, Ash. I'll provide a brief clinical update on BEST1 program. For reference, the data we have presented to date at Macula Society and ARVO are available on our website on the BEST1 page. We've completed enrollment in cohort 1 of the phase I-II study with five participants, including two autosomal recessive and three BVMD participants. You'll see that the BVMD participants are significantly better at baseline, with participant 102-102 being the least advanced participant from a visual acuity standpoint. What I'd like to really show you today is some of the phenotypes on the OCT that we're selecting for. This is being selected with a number of our colleagues in the field and has really been a great process for ensuring that we get the right subjects into the trial.
This participant is 101-106, and this is a representative BVMD patient. You can see that the participant has a pretty intact foveal depression, along with the retinal layers being intact in the periphery, both on the nasal and temporal side. Under the fovea and extending particularly to the temporal periphery of the retina, you can see the subretinal fluid that is part of the vitelliform lesion. This fluid is low and diffuse, and it's on the backside of the neurosensory retina, which is detached. Importantly for these patients, you can see those small areas of hyperreflective material, which are so-called shaggy photoreceptors, which indicate the photoreceptor outer segments may still be present. This is an important differentiation from the so-called effaced backside of the neurosensory retina.
We do expect that the product, if it works, should be able to decrease the amount of fluid under the retina, under the fovea, and as that fluid decreases and the retina is re-opposed to the RPE and Bruch's membrane complex, there is a potential that there might be a functional benefit for this patient. We also may potentially see that the ellipsoid zone line, which is present in the periphery of this image, begin to expand back out into the center of the macula, which would be fantastic for this patient. That would be expected to result in an increase in visual function. When we test visual function, we're testing really four different parameters. One of the most interesting to our team is the microperimetry.
What I'd like to see here is the overlay of the microperimetry on the infrared image of the OCT that we've already shown on the prior slide. Essentially, the OCT and the infrared image on the prior slide can be directly overlaid onto a map similar to what you see here. What you notice is that the areas of subretinal fluid that were present on the last slide on OCT are highly correlated with depression on sensitivity map on this slide. Therefore, in the areas where you see zero decibel sensitivity or a sensitivity of, say, less than 20 or so decibels on the heat map, you would expect the sensitivity of the retina to improve as the subretinal fluid in those areas goes away. That would be the hypothesis we're trying to prove in this study.
The ability to overlay the pathology and the modification of the pathology with this functional endpoint is a very unique thing for this program, and it allows us to test functional improvement of the retina at a very high spatial resolution. This is an approvable endpoint with the FDA, the improvement in these spots on microperimetry treatment would be acceptable as a potential pivotal endpoint. Obviously, we're still collecting all the other functional data, this is a very unique thing for this program that we're excited about. This is why we're looking for patients with fluid that correlates with visual functional improvement. If we're successful in decreasing the fluid and there are photoreceptors present, they sh ould function better if they're in their native configuration.
This, we hypothesize, should lead to an improvement in multiple functional endpoints, and most notably, as I've shown here today, potentially in microperimetry. At this point, I'd like to turn the call over to Joe Schachle, our Chief Operating Officer, to discuss the patient journey and the epidemiology of these IRDs.
Thank you, George. Good morning, everyone, and good afternoon to those in Europe and elsewhere. Two topics I'd like to touch base with you on. First is the IRD patient journey. I'll give you a brief overview of the patient journey. You heard a little bit of that this morning earlier. Then also talk about the disease prevalence, global disease prevalence, which you've seen in each of the individual presentations, we'd like to show you all together as well. Looking at the patient flow. As you heard, patients will often see an optometrist or a general ophthalmologist then be referred to a retinal specialist. That retinal specialist may make the diagnosis, may refer to a specialist that specializes in IRDs or a genetic counselor for genetic testing.
This is a very key step and something that we all need to support is the genetic testing aspect. If you look at the green bar, if you move to the left side of that's a patient that has a gene that we have a potential to treat and has been identified. Currently, RPE65 is the only one we have to treat and look forward to being able to add to that in the future. That's kind of a general view of how patients may move from symptoms to diagnosis to ultimately treatment. Thinking about global estimates on prevalence. Originally, we used two primary sources for global incidence and prevalence. The first was the Stone paper, which is an excellent study. It's a 1,000 IRD families being treated at one site from across 40 states.
It's very helpful. The Hanany study is also very helpful. It's a global study looking at six markets outside of the U.S. That was initial data that helped us estimate prevalence. Since then, we actually have asked Triangle Insights Gro up to prepare analysis and meta-analysis of studies, and they completed that in the first quarter of this year, and that's what you're seeing data here in a moment. That meta-analysis originally looked at over 1,200 studies. Of those 1,200 studies, greater than 90 qualified for use in this study. They need to have genetic testing as a backbone to the actual study itself. We looked at five geographies, the U.S., EU4 plus U.K., China, Japan, and Middle East, North Africa. Just taking a look at across the globe here. Let's focus on the U.S. first.
We kind of generalize that we have small, medium, and large prevalence diseases we're focused on. If you look at LCA5 and NMNAT1, those are our smaller prevalence diseases at 170 and 1,200. If you think about the mid-size disease, we're looking at RDH12, MERTK, and CNGB1. Those are on the 2,000 range for prevalence. Then finally, we look at BEST1 and RHO as the larger prevalence diseases at 8,400 and 8,800. As you heard in some of the previous presentations, looking Middle East and North Africa, you can see RDH12 with a prevalence of 17,500, so fairly large population, and MERTK at over 14,000 patients. Moving to China, you see RHO has almost 15,000 patients, and RDH12 has almost 10,000 patients. You can see across our globe, there is substantial medical need for treatments for these diseases.
One final slide here, this tags into some of the things you heard earlier is there may be underestimation of the actual prevalence of some of these diseases. If you look at our current BEST1 prevalence, we're estimating about 8,400 patients with BEST1 in the U.S., and that's based on studies that have confirmed genetic testing in the diagnosis. If you look at the right portion of this slide, we may be underreporting BEST disease, and there's 2 factors for that. First is while most patients do get genetic testing, because of the vitelliform and egg-yolk look of BEST1, some patients may not get tested because they may be assumed to be BEST1 and currently no treatment available.
The flip side of that is actually the misdiagnosis with BEST1. We're in the midst of a market research study right now, a large market research study, we're hearing quite frequently about the misdiagnosis. I'm going to read quickly this quote to you. "Quite a few of my best patients have been seen by other physicians in my practice and did not get the diagnosis of BEST1 disease. I think there are a lot of patients who are not diagnosed correctly, I would say about 50%." We are hearing this consistently across this study that there's a misdiagnosis and lack of diagnosis for BEST1. We may actually have some higher rates of prevalence than we have estimated currently. Thank you for your time. W ith that, I'll turn it back over to Ben.
Thanks, Joe. Now, in addition to Dr. Bennett and Dr. Leroy, we are pleased to have joining us today Dr. Todd Durham, Senior Vice President of Clinical and Outcomes Research at the Foundation Fighting Blindness. Todd is responsible for overseeing the foundation's patient registry, natural history studies, and other clinical programs. Let's go ahead and kick off this session. I'll start with a question for Jean, since Jean, you have such a unique perspective given your history in the field and the LUXTURNA development days. If you could just give us a perspective, what was the state of play with respect to genetic testing then versus now, and what were some of the biggest hurdles and unknowns?
When we first started getting ready to recruit patients in 2007, we had gotten everything all together, gotten all of the approvals, the institutional approvals, the FDA approvals, then we looked out to try to find patients. Where were the patients? Nobody, or very few patients in the U.S. had had genotyping because there was no reason to get genotyped. There was no treatment, no clinical trial available. It was thanks to our colleagues in the European Union that we were able to start. Our first four patients came from Italy, where they had made great progress in genotype-phenotype correlations, and several of the next patients came from Bart Leroy's site in Belgium because he had also been genotyping patients. Now the situation has changed dramatically.
There are now numerous sites, physicians genotyping patients because there are treatments, there is the LUXTURNA treatment available, and there are clinical trials available for many of the other forms of IRDs. Plus, people are anticipating the clinical trials that are being developed by Opus Genetics.
Got it. Yeah, sounds like night and day difference. Well, that's great. Thanks, Jean. To dd, a question for you, since the Foundation offers a free genetic testing program, could you walk us through the history of the program? How it might differ from others, and what are some other resources available for doctors and patients?
Yeah, sure. Thanks, Ben. The Foundation Fighting Blindness has had a registry study, My Retina Tracker Registry, since 2013. In 2017, we received a grant to try a pilot study to provide genetic testing and counseling to a small number of sites, really the centers of excellence at that time, to see what the uptake would be as a pilot study, it turned into an amazing success. We now are able to offer at no cost genetic testing and counseling to patients with inherited retinal disease in the U.S. We have hundreds of eye care professionals, including optometrists, low vision specialists all over the country who are ordering through the program now. At this point, we have tested over 32,000 individuals as of the end of March. It's a huge program, I would say wildly successful.
I think from the Foundation's perspective, we're opening access to patients all over the country, not just those who have access to a specialist center. That makes a huge difference when it comes to recruiting for clinical trials. This pro gram is just one of many that exist today. It has always been, well, most recently has been an option in the clinical setting to access and test for those individuals who have insurance coverage or able to afford a cash pay. There have been other programs over the years offered by commercial labs. The National Eye Institute had their own program for many years. I would estimate that at least half of the individuals in the U.S. with inherited retinal disease have had access to a genetic test by now.
I think this is going to be a program we will continue to need because not everyone will have access to a test at no cost or free.
That's great. I'm always astounded at how fast that registry is growing and how many tests you guys have provided. It's really remarkable and really moved the field forward. Great work. Bart, Dr. Leroy, since you sit in a different geography in Europe, in Belgium, what's been your experience with genetic testing? How does that work in your part of the world, and what percentage of your IRD patients have confirmed genetic diagnoses?
Well, thanks, Ben. It is the culture of how to organize societies, indeed very different from one side of the Atlantic to the other. Taxation is far less in the U.S., more money is given through grants and so on. That is certainly less in the EU, where taxation is higher, but the tax is used, for example, for national health services. For example, in Belgium, but not only in Belgium, in many other countries, we have a fairly free or nearly free, or if you're a clinical geneticist, which I also am, I can offer free genetic testing to our patients. Basically, everyone who walks into the door or through the door with a genetic diagnosis gets genotyped. Obviously because of the constraints of what testing currently is, we do n't do yet whole genome sequencing on everyone.
I would safely say about 70% of the patients gets their genotype, but everyone gets the opportunity, and they generally don't pay EUR 1 for it.
Got it. That's great. It sounds like basically everyone in your practice with an IRD has at least had access to a test.
It's true. I'd love to actually add to what Joe is saying, because if you look at, for example, the bigger European countries, don't forget, if you take the U.K. plus the E.U. currently, because the U.K. left us, together, it's 550 million people. I think that in the U.S., there are 335 million people. I think if you look at the whole of the E.U. and certainly the western part of the E.U., they have really good molecular programs. For example, for bestrophinopathies, I would certainly say that there are many more patients in the E.U. than there are in the U.S., and as he was rightfully saying, there are many underdiagnosed.
Yeah. Great point. Well, let's transition over to natural history studies and thinking about how it affects clinical trials. As we know, every IRD has its own clinical natural history, and there's even genotype, phenotype correlations or non-correlations that can complicate the picture here. Maybe, Jean, starting with you, how do you see how an understanding of clinical natural history affects clinical development plans? For example, how that helped in the development of LUXTURNA?
Well, when we started planning towards a clinical trial for LUXTURNA, we started doing a retrospective natural history study for RPE65 because there was no information, and it would've taken too long to do a forward planned study. That natural history study was run by Daniel Chung, who went to numerous centers, including Dr. Bart Leroy, and other centers around the world to collect this data. The data was extraordinarily helpful. It demonstrated that contrary to some people's hypotheses, this disease is not stable, that it does progress and the photoreceptors degenerate, and retinal pigment epithelium degenerates over time. It's relentless. It confirmed that the various outcome measures that are used to monitor retinal degeneration, the standard clinical measures such as visual acuity, visual fields, et cetera, light sensitivity decrease over time.
That data has been really important, not just in the early stages of the trial, but also in following the durability of the treatment. We're now looking at long-term durability and comparing that to what one would normally see in an untreated patient and seeing big differences.
Right. Great. Deviation from natural history is a clear sign of efficacy, I guess.
Yes.
Yeah.
Yes.
Thank you. Todd, at the Foundation, you guys have been running these really large, multi-center longitudinal studies. Some would say these are the gold standard in the field now. Can you talk about the Foundation Fighting Blindness Clinical Consortium that you guys are running, your approach, and some of the benefits of a multi-center versus single-center study?
Sure. Yeah. The Foundation Fighting Blindness Clinical Consortium is a collaborative network of inherited retinal disease specialists, reading centers, and geneticists to help us better understand inherited retinal disease. I would say from the Foundation's perspective, the primary purpose there is to better inform better clinical trial design, selection of outcome measures, length of follow-up that's required, finding the best opportunity for therapeutic intervention for various modalities. The largest of these that we've completed to date is the USH2A study in non-syndromic and syndromic USH2A retinal degeneration. We've had numerous papers about that. I think what makes it unique is the investigators. This is intended to be collaborative. I think the benefit here is we share the learnings across the centers.
I think from a data perspective, a single-center offers one advantage when it comes to clinical development, especially for subretinal injections, things like that. Many of the larger IRD trials and programs will require multiple-centers to recruit sufficient participants for rare disease. We need to know how to run those studies so that they can be generalizable and maintain the quality. That's a big focus of ours is to use standard protocols, same images and equipment, reading center methodologies, and to develop and to publish those results so we have lessons to learn to share with the whole community.
Super helpful for any sponsor in the space wanting to run a trial. That's really, really helpful. Real quick, could you also just talk a little bit about the Uni-Rare study? I know Opus is sponsoring a couple of arms of that study for RDH12 and BEST1. Any updates there?
Yeah, just briefly. The Uni-Rare study was our answer to trying to streamline the startup process for natural history studies where we'd already launched a study in EYS-associated RP that essentially using same protocol and procedures as the USH2A study. Dr. Sahel from UPMC said, "Why do we keep doing the same startup process? Let's develop a protocol that where we can do a plug and play." Bring in gene-specific cohorts and run with those rather than having to put the sites and all of us through all the pain and hassle of having to do all the protocol review and IRB submissions. Uni-Rare was intended to target the most rare of the IRDs because they've got relatively little attention in other studies.
As you mentioned, Ben, we are partnering with Opus Genetics on a BEST1 cohort of Uni-Rare and one for RDH12. These two cohorts illustrate the unique design of Uni-Rare, which is a very large cross-sectional study we're calling the registry component of the study where we have planned enrollment of 1,500 individuals. This is really just an opportunity to get a good phenotypic characterization, a cross-sectional look, including images that we can then send to the reading center. That's in the case of Opus, the BEST1 cohort. Then as we receive funding interest and prioritization for cohorts to follow longitudinally, we can then plug those into the longitudinal protocol and follow people annually up to four years. In the case of Opus, that's the RDH12 cohort.
The latest update on those is we have 65 enrolled in the BEST1 cohort with Opus and 19 enrolled in RDH12, and we're beginning to bring in the RDH12 participants to year two.
Great. Thank you, Todd, for the update. We're really excited about that work.
We are too.
Real quick, lightning round. One last sort of question for each of you, starting with Jean. What's one actionable step you think sponsors and sites can take together tomorrow to improve recruitment and retention in IRD trials?
I think one possibility would be to make genetic testing available on commercial platforms or patient-oriented platforms such as 23andMe and not just patients, people who are interested in looking at their own genetics might make it more available.
Got it. Bart?
Yeah, I think certainly there's a difference. I think having genetic testing, like Jean was saying, in the U.S. a little bit more accessible despite the unbelievable actions of FFB. I'm a real big fan of FFB, and you can see that initiative from large organizations like this help enormously. I think patient retention is not as bad as I think the numbers that were shown are in the sense that it's not my experience across 13 different gene therapy trials that we're currently running in Ghent that we lose many patients. It's actually by all means just here and there, maybe one individual. I basically think that getting them in would be better, as Jean was saying with what she mentioned.
Maybe if you want to do even better is really helping sponsor the activities of what FFB is doing because I think the Uni-Rare study is the way to go for the future.
Thank you. Todd, bring us home.
Yeah, I think in addition to those comments, I would say hyper-focus on the needs of patients and their families regarding trial participation, communication about what clinical trials are, making sure they have assistance with any translation or interpretations that they may need when they visit the site. I think this is all pretty standard in the IRD field now, but really focus on that experience for them. This is a tough decision for people t o participate in a clinical trial.
Yeah. Great. Perfect. Thank you very much to all of our panelists for sharing your thoughts on this important topic. Now we will transition to our final Q&A session, where we will be joined by the rest of our speakers. As a reminder, you can submit a question using the Ask a Question button on the top right corner of the screen, we will get ready for our first question. That is, I think I'll send this to Jean, actually. Can you comment on the expected duration of effect of a single treatment?
The best information I have goes to LUXTURNA, where we started out studying dogs, and the longest we followed was the life of a dog, which was 10 years. We showed that that rescued the photoreceptors in the treated area of the retina only. We're now following patients in long-term studies. In fact, the LUXTURNA studies go for 15 years of follow-up. That's a long time, and we are at the 10-year mark. That data has been Submitted for publication, should be out shortly. It looks very promising in that the durability data is excellent.
Got it. Quick follow-up to this for Ash. There's a question about the MERTK animal model slides where it looks like the effect is waning at the latest time point at 71 days. Is there something you'd comment there?
This was a preliminary proof of concept study and further dose optimization, further readouts are necessary to confirm the true window of treatment and durability. That's an effort that's ongoing right now.
Great, thanks. All right. Are the other IRDs besides BEST1 also likely to be underreported? How are the general dynamics in genetic testing and diagnoses for IRDs? I'll take a volunteer for this one.
Ben, I'm happy to talk about the BEST1 or the question on IRD frequency. I think others may be underreported. That may be the case with some of the other IRDs because there are so few treatments. However, we really have the most data on BEST1 because of our quantitative market research. I really can't speak to as much to the other ones. Maybe some of our key opinion leaders have an opinion on that.
Got it. Anyone want to chime in on that before I transition?
I can do so if you want to.
Yeah.
I think Joe's right. Bestrophinopathies are probably highly underreported. Some of them have been seen from clinics that treat uveitis patients, et cetera. Even patients who are just not aware that they have anything. I think that other IRDs are underreported, but probably at lower numbers. I'm pretty certain there are patients, even in developed countries like the EU countries and the U.S., where still patients even with night blindness, and some visual field issues roam around without understanding that their disease is actually a retinal degeneration. There's an underreporting certainly ongoing. I think many people will still not get to a specialist, but I think the numbers are particularly high for bestrophinopathies.
All right. Thank you. Question for Ash. Let's see. Hang on. For BEST1 gain-of-function mutations, would it be possible in the future to test a silence-and-replace strategy similar to RHO?
Sure. While that's not in scope for Opus now, silence and replace and editing could be possible for gain-of-function mutations in the future.
Okay. Thank you. All right. Regarding the 24-month update for LCA5, did improvements in BCVA translate to benefit observed in the virtual reality mobility test at month 24? Probably a question for Sally.
Sure. Yes, it is. With all three patients, they all had a meaningful improvement in their virtual maze object recognition.
Great, thank you. All right. What is the proportion of LCA5 patients would-be candidates for treatment, and how long is the treatment window for most patients? Do you want to take that one also, Sally, or maybe one of the KOLs?
It's down to the ONL preservation. A lot of these patients have preserved ONLs quite late on in the disease. Up to in their forties and fifties. I would say that it was a large amount of the population. Bart might be better to comment. However, those are the patients that we'd be targeting. We'd be targeting those that had preserved ONL.
Got it. Makes sense.
Sally, I can just comment that what you just said. In the interest of briefness, you're absolutely right. I think a large chunk of the patients would be treatable because they have preservation of some meaningful cells that can be targeted until fairly late in life.
Thank you. This one's probably good for George. In BEST1, how do you think about treating patients whose lesions do not yet involve the fovea? How can benefit be assessed in these patients?
Well, this is one of the beautiful things about the microperimetry. This is kind of the key point of the microperimetry, is that the grid overlay can identify the retinal sensitivity directly over where the lesion is present. For patients with extrafoveal or parafoveal vitelliform lesions, you can look at the microperimetry grid points that are overlying the area of vitelliform material. Our natural history studies and our initial patients enrolled in this trial inform us that those should be depressed compared to retina without neurosensory detachment.
All right. Thank you. A question for Ash. Will the disease in the dish be part of the clinical workup? How much time cost does that add? How can you determine that the expression of wild-type BEST will be sufficiently high for any given mutation?
Sure. We're currently testing all mutations now, so we don't wait for the patient information or genetic testing to come in. We are testing all annotated mutations in this disease in a dish model to understand which mutations are loss of function and which are likely candidates for gene therapy. In those tests, we're able to directly interrogate using in vitro cell models that resemble BEST1 disease pathology, whether we can restore BEST1 channel activity to that of wild-type BEST expression. That is a proxy for expression, but also directly measures function. We think that's a decent predictor of what could happen clinically and which patients are going to likely be responders.
Great. Thank you. Next one is, given the recessive ARB subtype is mechanistically cleaner than the dominant BVMD subtype, would you consider splitting the two into separate timelines so the ARB program can keep moving even if BVMD optimization takes longer? Someone from the Opus team, George or Sally.
Sally, why don't you take that one?
I think that, it will be down to, like I said earlier on, we take a data-driven approach. We'll be looking at the data, seeing how the patients respond following treatment, and then that will scope our strategy as to whether we continue with BVMD and ARB together or if we split out into two separate studies. It's something that we might consider, again, it will be down to the data and what we're seeing.
Got it. Thank you. All right. I think we're here at our last question, just about our last question. Based on manufacturing, how many patients can you treat once approved in initial three indications? First question on manufacturing, who wants to take that?
I can take that. The manufacturing has been a really productive discussion with the FDA. Just like we have been having the clinical discussions on trial size and endpoints for ultra-rare, we are also having the same type of discussion on the manufacturing processes. For the smaller programs, certainly for LCA5, a single 50-liter batch will treat a majority of the world's population, right? We are delivering 300 microliters through the subretinal injection. For LCA5, the manufacturing is quite modest. For RDH12, MERTK, RHO, those programs are a little bit bigger, but still should be well covered by 50-liter batches. As will Best disease.
If the upside of Best disease that Joe talked about, it turns out to be true, then certainly, we will start to get up to needing more than one batch and having to make multiple batches, which, in our experience with BEST1 should be very doable. It is important to remember part, a big part of the thesis of OPUS is not just clinical efficiency, but it is also on the manufacturing side. I think Dr. MacLaren mentioned this earlier. That is one of the reasons why we are using pretty well-known vectors, well-known gene augmentation techniques, is because these things can be readily manufactured. Now the world has now a couple decades of experience, thanks to some of the pioneering work by Dr. Bennett, and the University of Pennsylvania team years ago.
Great. Thanks, George. I will do one more quick question, George will make some closing remarks. This is to Dr. Todd Durham. Can you just talk a little bit about how Foundation Fighting Blindness as a patient advocacy group works with the FDA to help move the field forward?
Yeah, sure. Happy to, Ben. I guess the best example is from our USH2A study. We had several meetings involving the FDA and the European Medicines Agency to share our learnings from that. One of those things, I would say, resulted in a Duke-Margolis meeting in September 2025, primarily about our findings and recommendations about the FST. I think where we ended up with that is the FDA currently is not ready to accept that as a primary outcome measure for inherited retinal disease trials. That has, I think, informed our decision to develop a strategic plan to provide the missing evidence around clinically meaningfulness for that outcome measure and others for inherited retinal disease. That is work we are undertaking now, having gotten a lot of input from our key opinion leaders and experts on that.
We intend to continue our dialogue with the FDA and EMA and other regulators as we learn about novel endpoints. We're also advocating for patients through patient-focused drug development meetings as we go through time. It's an active engagement, and we're pleased to collaborate with them.
Great. Thanks, Todd. Appreciate that. Thanks everyone for that Q&A session. I'll now like to turn the call over to George for some closing remarks.
Thanks, Ben. Let me just summarize what's special about Opus. Number one is it's proven science. Number two is that we're uniquely well-capitalized to execute against multiple programs. Number three is that we do have multiple shots on goal. Number four is that there are real near-term significant value inflection points, multiple within our current runway. I'd like to thank everyone for your time and attention this morning, especially a big thank you to our guest speakers. What an amazing panel. I mean, really an honor to be a part of. For adding, thank you for adding your insights and your expertise. We look forward to updating everyone on our progress as we continue to advance our gene therapy pipeline and continue to hopefully bring these innovative therapies to patients. Have a great day.