Hi, everyone. I think we can go ahead and get started. Welcome to the Jefferies Global Healthcare Conference. My name is Aarav Jagrup. I'm part of the Healthcare Investment Banking team, and it is my pleasure to introduce Mr. George Magrath, the Chief Executive Officer of Opus Genetics.
Hey, thank you, and thank you to the Jefferies team, and thanks for everybody for coming today. We're going to talk a little bit about Opus Genetics, and then we'll have time for questions as well. Opus Genetics is an ophthalmic gene therapy company founded out of the University of Pennsylvania from the assets of Dr. Jean Bennett and others. There are a few core principles through these assets which are important to realize. One of which is that these are going after diseases where we expect to see a quick improvement in vision, and so the trials end up being very fast. We expect three to six months or so of treatment should give us some sort of benefit, and that's exactly what we saw in the first clinical program that I'll show you data in. First two clinical programs I'll show you data in.
The second is that these are all delivered to the eye, so off-target toxicity, systemic effects are much less of a concern than with systemic gene therapies. With it being delivered directly in the eye, it's also small volumes, so manufacturing is much more modest than you would expect for other gene therapies. There are a number of core principles of this company which lead to streamlined timelines and very capital-efficient development, and for that reason, we're able to develop a number of these in parallel. Now, the subretinal injection is really important concept here. We're delivering 300 μL of the gene therapy under the retina directly to the photoreceptors in RPE, exactly like LUXTURNA is delivered. This is probably one of the most precise deliveries of medicine in the human body with off-target effects that are very modest.
The second principle that we talked about, remember, was the ability to show a quick treatment effect. This comes from the idea of structure-function dissociation. This is another idea from Dr. Bennett, and really was the crux of her invention of LUXTURNA. Structure-function dissociation really means that the structure of the retina is present, however, it's not functioning because it's missing a protein. We're using pretty straightforward gene augmentation techniques to go after a retina structure that is normal but not functioning. In LCA5, it turned on the function of that retina within a month. By three months, there were multiple log units of sensitivity above where they were at baseline. What this means in the real world is, A, the trials can be quick.
We don't have to wait years to look at progression or anything like that. Then B, the effects can be dramatic. As we saw in the LCA5 trial, it was featured on Good Morning America. It's making dramatic improvements in these patients' vision. We have seven of these gene therapies, all of which are heading into the clinic, all of which are being developed. We are going to be delivering pivotal data in the not terribly distant future for LCA5. We're going to be delivering first-in-human data on BEST1 in the imminent future, this summer. Then RHO, RDH12, MERTK are all going to be treating patients in the near term, along with NMNAT1 and CNGB1 after that. The mantra here that we have is really these programs are about $30 million and three years from an IND to a BLA.
If they work, they go very fast. If they don't work, they can also be killed very fast with minimal sunk cost. We also have a commercial partner program, which is an eye drop for presbyopia. The PDUFA date is in October for the presbyopia asset. That is partnered with Viatris for commercial rights. We enjoy about $100 million in milestones and a double-digit royalty that tiers into the 20s. We have a true non-dilutive source of capital to help fund this thing. You'll see that later in the presentation, and our Chief Financial Officer is here if you have questions on it, but our runway is into 2029 with all of these programs going forward, which is going to mean that there's capital to execute against multiple data readouts in the next few years. It's going to be a really busy, really fun time for the company.
The two most near-term assets that we're going to be reading out are BEST1 and LCA5. BEST1 is really a pretty blockbuster indication. It's around 8,500 U.S. patients. Again, 8,500 U.S. patients with no treatment, to give some comparables for pricing, LUXTURNA is priced just under $1 million per patient, then gene therapies for systemic conditions, as you guys know, are $3 million-$4 million or so. Somewhere in that range will be what we would expect for the value of our assets, obviously based on the efficacy and safety that we provide to patients. BEST1 is a disease where you are missing a calcium-activated chloride channel in the RPE, the retinal pigment epithelium, that leads to the accumulation of visual cycle byproducts under the retina called a vitelliform lesion.
This leads to subretinal fluid, essentially very similar to what you see in a wet AMD or a diabetic eye disease. However, it's not vasogenic, so the anti-VEGF agents do not work for this. It is from the byproducts of the visual cycle. We are simply restoring that calcium-activated chloride channel. When we do that, we would expect that the fluid would be resorbed in a more normal way, leading to a more normal architecture of the retina and those photoreceptors that are present there to function better. This disease is something that we are going after in a phase I/II trial currently, and we're going to be presenting three-month data on the first five patients in September of this year. LCA5 is much less common. It's around 200 patients in the U.S., a little bit less than that. We have remarkable results in this disease.
This is a disease of early childhood. These patients go blind at the age of one to two- years old and live a life of reading braille and needing assistance. It's a profoundly debilitating disease. What we've done so far is treated six patients, three adults, three adolescents, all with severe disease. We have seen what the University of Pennsylvania at the recent ARVO conference described as normalization of cone photoreceptor sensitivity in these people. It's been a really remarkable improvement across all of our endpoints. That trial is heading into a phase III component right now that we expect would be sufficient for the application of a BLA. These IRDs are rare, but they're not ultra-orphan with the exception of LCA5.
You can see here that in the U.S., you've got two programs that are closer to 10,000, and you've got the remainder of the programs just around 1,000 patients to 3,000 patients. Enough patients, again, remembering that an IND to a BLA is about a $30 million exercise, plenty of room to create a very viable business plan for the company. Interestingly, look at the ex-U.S. numbers. For example, RDH12 and MERTK in the Middle East. MERTK is actually going to be funded by the Department of Health in the U.A.E., in the Gulf countries. That really has to do with founder effects of the genetics. Importantly, in the Middle Eastern regions, in the developed countries in the Middle East, they reimburse for LUXTURNA comparable to the U.S.
If you look at the ex-U.S. numbers, looking at the EU, the Middle East, you can really start to create a nice walk in your model to something that's above the market cap of the current company. Let's talk first about BEST1, though, because BEST1 is our biggest indication that currently has a readout in the next few months. We talked a little bit about the biology here. What I want to talk about is the gene therapy, which is an AAV2 capsid, which is the same as LUXTURNA. It's trophic for the RPE, and it has a native BEST1 promoter in it. Even if there is off-target effects in photoreceptors or such, the BEST1 promoter is only turned on in RPE.
Again, this is a calcium-activated chloride channel, and if you lose that chloride channel, just like on the right side of the screen, you see that there is a loss of the osmotic gradient that is responsible for pulling the fluid out of the retina. You get the accumulation of that fluid and micro detachments of the retina. This is exactly what you see on the OCTs. If you look at the stages, when you get to Stage 3 and Stage 4, you're seeing significant fluid under the retina with preserved photoreceptors over that. Our hypothesis is if you can have that fluid resolve and those photoreceptors sit back in the natural configuration, like you see on the top OCT, that you should improve the patient's vision and their ability to function. As they get into Stage 5, you do see more atrophy and fibrosis.
In the patient that was presented at The Macula Society meeting by Dr. Pennesi in February, that was a pretty severe Stage 5 patient, even that patient had 12 letters of vision gain. Really remarkable. What it meant for that patient, that patient went from being able to only see fingers in front of her face to being able to almost see on the eye chart. Really cool. Why do we believe this might work is we have evidence from a naturally occurring dog model where if you inject this gene therapy, that fluid under the retina goes away. You can see that demonstrated in the OCTs at the bottom. The first two OCTs are in a control group. The second two OCTs are before injection and then out to 103 weeks after the injection.
Really, really interesting canine data that was published in PNAS in 2018. What we're doing now is a dose escalation phase I study looking at safety, right? We're looking at very severe patients, a mixture of dominant and recessive patients, and we're looking for safety, and we're looking for some signs of efficacy, and we're looking for, in particular, structural improvement of the retina. It'd be great if we compare that with an efficacy signal as well. One thing that's interesting about our study is that once we see that efficacy, we have the ability to flip it into a pivotal trial. If we don't see the efficacy we want, we have the ability to dose escalate and treat at about a 4x higher dose.
It's really an interesting trial design that is optimized for efficiency. We have enrolled the first cohort, and you can see the demographics here. These are later-stage patients. As we get further into the cohort, you can see we're walking down the age group into what are most typically the presentation of the disease, which is in the 30s or 40s, in decades in life. You can see that the baseline visual acuity is pretty poor in the first patient, but in the next few patients, it's somewhere between 20/70 and 20/150 or so. It's pretty diminished vision, but still good enough to expect to have photoreceptors that are viable. If you look here at an example of the OCT, this is patient 06. What you see here is exactly what we were talking about.
That lesion in the macula with some low-lying fluid over the lesion, with photoreceptors still viable on the backside of the retina. That correlates very nicely with deficits of microperimetry. Microperimetry is a test where you shine a light at each one of these points on the retina. As you shine that light, you have the patient respond when they can sense the light, when they see the light. You can actually map out the sensitivity of the photoreceptors and the function of those photoreceptors to a resolution of maybe a quarter of a millimeter. It's a very precise way of testing the function. The beautiful thing about this disease is where that fluid is exactly where you see the deficit.
You're going to be able to watch this test over 3 months-6 months, and hopefully that test will begin to improve as the photoreceptors lay back in a normal configuration. This is an FDA approvable endpoint, and so this does have precedent at the agency as being a pivotal endpoint. We have reported the first patient. The September report will be four additional patients. This patient was a 63-year-old with the recessive version of disease, meaning that she lost her vision in the teenage years of life. For her, it was 15 she first noticed her vision was deteriorating when she wasn't able to get a license at 15, and subsequently went down and was a very visually impaired individual for essentially her adult life. It was a safe and well-tolerated treatment.
What we saw in the treated eye was an improvement over the first three months of 12 letters of vision. Now, the lesion in this patient was directly in the foveal area. You can see there's just a little bit of fluid left in this patient. Again, this patient was like a Stage 5, so mostly atrophic. There was an area of fluid that disappeared after treatment, and I think that that fluid resolution led to an improvement in her vision. It was a really great first. It's only one patient, so I don't want to oversell it, but it was a great early sign of efficacy. We're going to report out the remainder of the four patients in September, and then either dose escalate or flip it into a pivotal trial. That's coming up very fast, and we're looking forward to that readout.
LCA5 is, again, a disease of childhood, and this patient that's pictured here is now in his late 20s and was one of the subjects in the study. LCA5 is a disease where the structure of the retina looks pretty normal. That's actually what Leber congenital amaurosis means, is that when you look into the retina, it looks fairly normal when they're a baby. That plays really well into the structure-function dissociation. The structure of the photoreceptors is normal. However, they're not functioning. The reason they're not functioning is because they're missing a protein called lebercilin, which is responsible for elongating the outer segments of the photoreceptors. If you guys will recall from your cell biology, the photoreceptors are long rods and cones, so they're elongated structures, and they rely on lebercilin to keep them in that elongated structure.
If the lebercilin is gone, they kind of accordion down on themselves, and then they can't depolarize with light. When you replace the lebercilin, you would expect those outer segments to elongate back into a normal configuration and be able to sense light. That's exactly what we saw in this trial of 6 patients, and you can see here that these patients were either young adults or adolescents and were very visually impaired at baseline. Over time, I'm going to show you a number of endpoints. Over time, you're going to see improvements in all of them. What you're looking at on the left of the slide is the adults, and we have 18 months of data for the adults, and the kids on the right, which we have 6 months of data for. This first is just their visual acuity
It's presented in LogMAR visual acuity, and the reason it's in LogMAR is because these patients are off-chart. You can do it in letters equivalent, but really, until after they're treated, they can't see letters on the eye chart. One of the cool anecdotes from one of these patients was that they actually were able to get on the eye chart, and the doctor at the one-month visit said, can you read those letters on the eye chart? He said, yeah, I can see them. He said, what are they? He said, well, I've never seen letters before, so I don't know what they are. He had to learn what an E looked like. It's kind of cool. Full-field stimulus threshold testing is a global test of the sensitivity of the retina.
You shine a light at the retina of different wavelengths. On the left of the slide, you have the red wavelength of light. On the right of the slide, you have the blue wavelength of the light. On the top, you have the three adults, and on the bottom, you have the three children. What you're seeing here is a more than 1 log unit, and in the children's case, a 1.5 log unit improvement in the sensitivity of their retina. This test is the reason we flipped it into a pivotal trial at the low dose, because this is what the doctors would consider a theoretical maximum response in these patients. Really remarkable improvement in FST. Very important data set. This was actually the first improved endpoint in the LUXTURNA trials as well, so there's a correlate there.
You look at the maze, again, this is number of the objects that they were able to identify in the maze, and you can see a nice separation from the placebo here or from the untreated eye. Again, microperimetry. You can see here we have some data on two of the patients. Only two of them were able to complete the test because it does require fixation to be able to map the fovea and the macula. You can see here, what I would concentrate on is the amount of red. The red is the area they can sense of light, and you can see, obviously, after treatment, a pretty dramatic improvement. Around a 10 fold-18-fold improvement, depending on the time point you look at.
Again, we are in the process of working with the FDA on finalizing the phase III design, and that design, because this is ultra rare, will incorporate a run-in group as the control, and we are enrolling that, and we'll start the treatment once we have agreement on the design with the FDA. Again, the important thing to realize about this company is that these are all quick hits. we're able to take these life-changing therapies, develop multiple of them because we're going to know very fast, within six months or so, whether or not they work. That allows us, A, to limit some cost, B, to go quickly towards approvals, and C, to be very capital efficient. Our cash balance of $90 million gets us a runway into 2029 with all of these programs going forward.
That could theoretically get us through to the first approval. However, as you can imagine, we're going to have multiple data readouts for BEST1, for LCA5, for RHO, for MERTK, for a lot of these programs within that timeframe. It's a really exciting opportunity right now. With that, I'll take any questions that you guys may have.