44th Annual J.P. Morgan Healthcare conference

Jan 15, 2026

Morning everyone. My name is Susmita Roy and I'm an associate on the J.P. Morgan Healthcare Investment Banking team. On behalf of J.P. Morgan, I would like to thank everyone for attending the healthcare conference this year, and I'm pleased and honored to introduce Opus Genetics for their company presentation today. A bit about Opus Genetics. It is a clinical stage biopharmaceutical company developing gene therapies for inherited retinal diseases, trading under the ticker symbol OPGX. They have a multi-asset pipeline with near-term data readouts with many milestones in 2026. It's my pleasure to introduce the CEO, George Magrath, for the company presentation. I'll hand it off to him and we'll take Q&A right after. Thank you. Thank you, and thank you to the J.P. Morgan team for inviting us, and it's great to see a full room here. This looks wonderful. I'd like to take a minute to talk to you about Opus Genetics and what we're up to. This year is going to be a pivotal year for us. We have a readout in our biggest indication, which is BEST1 disease, which will happen in the mid-year. We've got the ongoing pivotal trial in the LCA5 program. That was the program that was featured on Good Morning America a few months ago. That's going to have additional data coming in the not distant future as well. We're looking forward to multiple additional assets hitting the clinic. It really is a good year. The Opus Genetics story is really interesting. It's very unique. It is a story that's based on Dr. Jean Bennett from University of Pennsylvania, along with a number of other collaborators of hers. We're looking at what we consider sort of low-hanging fruits. We're looking for diseases where the structure of the eye is normal, but the function's not, and it's not because a single gene is missing. That lends itself very well to straightforward gene augmentation, very similar to what Luxturna did as the first approved genetic medicine in 2017, also invented by Dr. Jean Bennett. In these AAVs, you're delivering a small dose directly under the retina, very localized, very precise, and looking at diseases where we're not trying to do long studies where you bin curves. These are studies where you should see an improvement of function, a reversal of the pathology pretty quickly, 3-6 months. It lends itself to efficient development. There are a number of these in our pipeline. You can see we refer to them as a string of pearls. The seven of them are at the bottom of this slide, and each of these is a very efficient, quick program that's been hand-selected for these reasons. When you think about this delivery system, it is I think the most precise drug delivery in all of medicine. We're delivering a 300 microliter bleb under the retina. Really, like in our BEST1 program, we're really only trying to transfect 5 or 10,000 cells in the retina. The exposure outside of the eye is negligible. The systemic side effects are negligible, and the ocular AEs are very well characterized. These are all AAV2s, AAV8s, AAV9s. These things have been used in the eye before. Our company is really more of a development company, not a discovery company. We pick things that we think are going to have high probability of success and are reasonable to show efficacy in efficient, quick trials. Now, the important key underlying factor to what we're doing is the concept of structure function association. In these patients, in these diseases, we're looking for patients that have almost normal anatomy, right? The photoreceptors are there, the bipolar cells are there, the Müller cells are there, the ganglion cells are there, the RPE cells are present. The retina structure is there, and the machinery is turned off for some reason. That is the structure function association. It lends itself very well to gene augmentation. It's almost like you're baking a cake and you're missing one ingredient. You put that ingredient in, and all of a sudden you're off to the races. The structure function association is important because it gives you a high probability of making a biologic impact. It also gives you a quick readout. When you reverse pathology, when you take these profoundly blind people and give them vision back, you see it pretty quickly. In these studies, we know whether or not we have a drug pretty quickly. Now, the pipeline is broad with these. There are seven of them. The key thing to focus in on is the fact that we typically use equity dollars to concentrate on clinical programs. Right now, those are LCA5 and BEST1. This year, it's going to be multiple others that are in this pipeline. The preclinical assets all have additional support to get them through the preclinical pipeline. The team led by Ash and others has been incredibly efficient at getting grant funding, getting partnerships with different patient alliances such as the RDH12 group that are bringing these things forward. It really is an interesting business model that is taking these things from the lab into the clinic. We have another unique aspect to the company, is which we have a commercial asset that's partnered with Viatris for sales. This asset is a topical eye drop called phentolamine ophthalmic solution. The brand name is Ryzumvi. It's on the market for the first indication, which is that it reverses dilation after an eye exam. Then we just submitted the sNDA for presbyopia, which is the need for reading glasses. If you put this eye drop in once at night, if you look at our phase III studies, people can then read without glasses for about 24 hours. It's a very interesting value proposition for people. This has been partnered with Viatris. We have a double-digit royalty that tiers into the 20s, and we have around $120 million in milestones on it. Viatris is a great partner. They have a large sales force, and we're very excited for presbyopia to potentially be approved this year. We're going to have a readout in BEST1, which is our biggest wholly owned indication. We're going to have a potential approval for presbyopia, and we're going to have an ongoing pivotal trial for LCA5, and we're going to have multiple of these preclinical assets entering the clinic this year. The team is busy. It's a lot of fun. Let's talk about two of the lead programs here and the upcoming milestones that we have for these. BEST1. These I'll talk about in some detail in a minute, but it's a large indication in the rare space. It's 9,000 patients in the United States. When you think about that epidemiology, there are around five or so epidemiological studies. The bookends of that are somewhere between 5,000-19,000. Using our methodologies, we're honing in on around 9,000 patients in the United States. This disease is a loss of a calcium chloride channel where you get a blister of fluid under the retina. If you replace that calcium chloride channel, then the fluid should go away and the vision improves. This trial, the phase I/II trial, is ongoing, and in the mid-year, we'll report data. The things to look at in the data are an improvement in the electrophysiology, so that the ability to have a calcium chloride gradient, a voltage gradient across the RPE, you can actually measure that. That'll tell you about cellular target engagement. If the fluid on OCT goes away, then that'll tell you about the macro structure. If vision improves, that'll tell you about the function. It's a really nice logical walk of endpoints that we'll be able to read out in the mid-year. LCA5 is a program where we have already treated six patients. All six of those patients have had clinically meaningful improvements in vision. One of those patients was featured on Good Morning America, because of how profound her vision restoration was. After a RMAT meeting in October, we have begun enrolling into the pivotal trial. The first two patients have been enrolled in a pivotal trial, and we're going to continue that this year, looking for data readout, not this year, but probably in 2027. These are actually big indications, and the reason I say that is because a first principle is that you get reimbursed for the improvement in patients' lives that you create. When you have a dramatic improvement, like taking a blind child and restoring vision, you can command reasonable pricing to make it worth your while. You can see here that the market opportunity is actually really good as long as the string of pearls stays intact. This is a very important slide because a lot of the preconceptions that gene therapy development is long, expensive, and with limited return is just fundamentally not true for Opus Genetics. We're going after very well-characterized AAVs, very well-characterized diseases, quick endpoints, small trials, meaningful impact that should be reimbursed in a reasonable manner. Let's talk a little bit more about BEST1. BEST1 disease is one of the most common IRDs that's out there. There are about 350 of these inherited retinal degenerations, and 3.5% of those have BEST disease. It's actually typically seen in regular retina clinics. The way the patient's journey goes with this is that it's in the midlife years, second to fourth decade of life or so. The patient will have mildly distorted vision, and they'll typically go to their optometrist. The optometrist will see the clinical exam, which is almost pathognomonic for BEST disease. They'll send them to a retina specialist to confirm that diagnosis. A lot of times, in my practice, I didn't even genotype these patients because you could make a clinical diagnosis of BEST disease, and there was nothing you could do for these patients. You would tell them to follow up once a year. Eventually, those photoreceptors will atrophy, and they will end up with a large area of geographic atrophy. Looks exactly like the geographic atrophy associated with macular degeneration. That's profound vision loss. You end up with this multi-year window of potentially intervening for these patients, where they're mildly symptomatic. The photoreceptors are still present, but they're detached from the retina, so they're kind of floating in this fluid. If you can resolve that fluid, the photoreceptors won't atrophy. They'll be back in their native place, and they can potentially see again. It's a really nice pathology to be able to intervene with. Large therapeutic window. Not much of the channel is needed to impact the disease, and it's very precisely delivered directly to the lesion. The cellular biology is really interesting with this. The bestrophin channel is a pentamer that creates a calcium chloride channel. The purpose is to put calcium on one side of the cell, chloride on the other side. Doing that creates a gradient which pulls fluid from the photoreceptors into the choroid, into the systemic circulation for disposal. As those photoreceptors, which are incredibly metabolically active, are continually to produce byproducts, that osmotic gradient causes those byproducts to be pulled out of the retina into the circulation. In Best disease, you lose that channel. That gradient goes away, and the fluid just accumulates under the retina. That's exactly what you see on these scans. On the right of this slide, where you see OCT, that is a cross-sectional view through the retina, and at the top on a pre-stage 1, that is essentially normal-looking. What you see is as the fluid accumulates, as the patients go from stage 2 to 3 to 4, you get more and more fluid. The photoreceptors now are on the backside of that fluid detached from the wall of the eye. If you look at the bleb of fluid, you've got photoreceptors, you've got RPE, and you've got fluid in between them. That fundamentally takes the photoreceptors away from their support system, from their nourishment. They are hanging out in the wind there. If they do that for long enough, they will atrophy. As they atrophy, they stop producing metabolic by-product. The fluid goes away, and you start to see that in stage four, and you see the conclusion of that in stage five, where you have atrophy, where the photoreceptors are gone, and you have total vision loss in that image where the black circle is in the middle of the autofluorescence image. There are two types of Best disease that are important for us to talk about. The first is BVMD, the second is autosomal recessive. Autosomal recessive is a very clear-cut gene augmentation target. There's no Best channel that's being made. Gene augmentation can restore that. In autosomal dominant disease, this is still a good augmentation target without the need to silence the mutant protein, because the stoichiometry allows you to outcompete the mutant, which is non-toxic in most cases, and form that pentamer. We've actually done a lot of in vivo disease-in-a-dish-type models at a patient-level basis, where we can show restoration of the function of that channel, with dominant mutations. The one part of this disease, one genotype of this disease, where we will not work is gain of function. In a recent publication by GeneScape, that accounts for around 2% of the BEST population. The AAV is very straightforward. It is a construct in an AAV2 that has the normal BEST promoter. Not only are we delivering it directly to the RPE cells in a very targeted fashion, the promoter won't even be turned on unless it is in an RPE cell. It's like a second line of safety for off-target effects. In a dog model, which is the data is shown here on this slide, what you can see, this is a naturally occurring dog model that was done at the University of Pennsylvania, published in PNAS, on the citation that's listed. You can see that blister fluid on the cross-sectional image, which is the image right below the picture. You see the pocket of fluid. In a control animal, that pocket just gets bigger. In a treated animal, that pocket literally goes away. You're looking at reversal of pathology in this disease. It's a wonderful endpoint. It's a wonderful view of target engagement. The retina specialists in the United States, every one of them does this scan on every patient that comes through their door. This is going to be very important to us as we try to show target engagement and modification of biology. On the histopathology right underneath that, you can see that the photoreceptors not only lay back down on the RPE, but they restore normal interdigitation with the RPE. It's almost like a handshake. It goes literally back to a normal configuration. Right now, we're doing a phase I/II trial. We're enrolling these patients in two cohorts, 1.5 E9, 4.5 E9, five per cohort, and we're going to be reporting the data in mid-year. We do think that even at the lowest dose, we should see target engagement. That target engagement we would know through electrophysiology at the cellular level, OCT at the macro structural level, and microperimetry and visual acuity at the functional level. Best disease is incredibly exciting. We'll talk a little bit about LCA5. It's a much smaller indication, but we have amazing data in this. This is a really impactful medicine. This disease is a type of childhood blindness where the typical patient journey is that these children are born with the mutation. Usually, mom or dad notices that the kid at age one or two can't really pick up a toy, can't see to pick up their Cheerios to eat, things like that. Take them into the doctor's office. The fundus looks pretty nondescript. These patients all get genotyped. They all end up at tertiary care centers. Honestly, most of them end up at the University of Pennsylvania. Of the 200 patients, I think 50 or so are seen at the University of Pennsylvania by Dr. Tomás Aleman, who's the world's expert in this. This is a profound blinding disease from early in childhood. However, for the first few decades of life, the structure remains normal. As in the nondescript fundus findings, when you look at these patients, typically the fundus looks pretty normal. The OCT has all the structure there. Everything looks good. Patient can't see. They have a defect in a protein called lebercilin, which is a structural protein in the photoreceptors that causes them to be in their normal configuration. The loss of lebercilin causes the photoreceptors to still be present, but not to be able to sense light. What we're doing is very simple. We're using an AAV8 with the same promoter technology as Luxturna to replace lebercilin in the photoreceptors. The reason this is AAV8, Luxturna is AAV2, is because of the target cells. Luxturna is targeted to RPE. This one is targeted to photoreceptors. At this point, we've treated six patients. All six have had clinically meaningful endpoints. In profoundly blind patients, you need to look at the endpoints across different types of modalities to be able to evaluate them. The first, and actually, honestly, the most unexpected, was that five out of six had a clinically meaningful improvement in actual visual acuity. First patient that I'll show you in a minute, this is an example, went from being able to just see shadows, like a hand maybe in front of their face, to being able to see the big E on the eye chart. Very profound type improvements. These gains were seen as early as one month, and so it's pretty fast to turn on the machinery. The durability that we've seen in the adults that we've treated so far is out to 18 months, and really, you sort of see a peak in efficacy at 3-6 months, with a duration at least out to 18 months at this point. FST is an incredibly important endpoint. This was the first statistically significant endpoint in the Luxturna trials in the 2010s. FST is a way to measure the overall sensitivity of the retina to light. It's a very good test. What we've seen here is a logarithmic scale improvement in FST and an improvement to what the investigators and the FDA consider to be sort of a theoretical maximum for this disease. The improvements in FST in these patients is the reason why we worked with the FDA to even at the lowest dose, to stop this escalation and go immediately into a pivotal trial. It's really remarkable on FST. MLMT. This is a virtual reality maze. This is a test where the patient puts on a headset, like a Meta headset, and they have the two little joysticks or the controllers, whatever you call them. They are presented a course that they follow in virtual reality world through the headset with objects that they tag. It's a very simple, elegant test, mostly of their peripheral vision. If visual acuity measures sort of your central vision, then MLMT is more of a peripheral vision test. What you'll see reported here is the number of objects that they could identify, and you do it at multiple luminances, which are all clinically significant. You start at like a starry night luminance, and you go to a full moon, to a normal conference room, to a bright conference room type lighting. You'll see that this was pretty meaningful. Safety was as expected. There were no ocular treatment-related serious adverse events. The six patients we've treated, you can see here, the main things to see on this, we started with adult patients. These are adults, literally like the 34-year-old patient, 0101, is the one that was on Good Morning America. She's 34. She's been blind since she was a little child. What you can see is with the LogMAR visual acuity, it's pretty severe. Now we are going into pediatric patients because we believe as you treat younger and younger patients, you have more of an ability to intervene and restore vision. We think that the results are probably going to be amplified in the pediatric population, and that's exactly what I'm going to show you in the coming data slides. The first is visual acuity. We measure visual acuity in LogMAR because these patients are off of typical eye charts. Actually, they jump between charts, and it's a little bit more nuanced to measure this low a vision. You measure it in LogMAR, and a kind of rule of thumb for the people in the audience that are familiar with ophthalmic trials is that for every 0.1 LogMAR improvement is about the equivalent, approximately the equivalent of five letters on an eye chart or one line on an eye chart. What you can see here in the adults is the orange line is the treated eye. The untreated eye is the more teal line, and you see a nice separation there that is seen pretty early in the disease and is maintained out to 18 months. In the children, on the right of the slide, we have much less follow-up. We only have three months of follow-up. But you see a more profound separation from the fellow eye, and you see a really remarkable 0.4 improvement in LogMAR visual acuity. That's really great vision. Patient-level data is available on our website if anybody's interested in seeing actually all six patients. FST is really interesting. FST, again, this is a logarithmic scale. When you look at the separation, you have to put this into a logarithmic type framework, not a linear framework. Red and blue is both different wavelengths of light, obviously, measuring different types of photoreceptors. Again, you see a separation that is clear, consistent, and durable. MLMT. This is the virtual reality mobility test. Again, this is the number of objects a patient could identify through the Meta headset. On the Y-axis, you see the number of objects. On the X-axis, you see time. Again, you see the adult cohort on slide left and the pediatric cohort on slide right. What we think is meaningful in this, based on some work done at Penn on the validation of this test, is that approximately a difference of about two or three objects is going to be the standard error. Microperimetry is really interesting. Microperimetry is a test where you can actually do a point-wise testing of the retina. It's almost like probing the retina to see the light sensitivity. On this image that you see here on this slide, you see a grid overlaid on the patient's retina, and then at every one of those black points, you test the sensitivity of light at that point. Only this requires fixation at baseline. Only two of our patients could actually complete the test. These patients had a remarkable improvement in the area of the retina that could sense light. The thing to concentrate on this is really sort of the heat map. If you look, for example, in the second column, that's the study eye. If you look under sensitivity, you see baseline is the first image with maybe three little red marks at one month, and then at 12 months you see something that looks like the continent of Australia, I think. Something like that. Much better. You see this also in one of our pediatric patients who could do this. Really remarkable test, that shows not only target engagement, but also shows functional improvement in these patients. At this point, we have excellent safety data. We have robust biological activity across every endpoint that we've tested. We've received rare pediatric, orphan, regenerative, RMAT, all the things. We have talked to the FDA, and we flipped this trial into an adaptive phase III trial that we're currently enrolling. We do have that partnership with phentolamine. I'll go very quickly through this. We're very excited about the sNDA for presbyopia. I'll tell you the differentiation here is that currently, the approved version of phentolamine, Ryzumvi, does not carry a warning label for retinal detachment or for issues with dim light vision. We think that this will be very well received for patients and a great product. We're looking forward to potentially having this approved this year. At this point, I'll go through a little bit of just the expected catalyst one more time, and then we'll open it up for questions. Again, the main thing to concentrate on is the BEST1 readout in the mid-year of 2026. Initial data will be at a medical conference in Q1, but that'll be very limited data. LCA5, we're going to continue dosing the phase III, and we'll provide updates on that. We think that at least two additional gene therapy programs will enter the clinic this year, and we're very excited about both of those. phentolamine, the second indication of presbyopia, we hope for an approval sometime this year. With that, we'll open it up for questions. I'll also ask the President of the company and Co-founder of the company, Ben Yerxa, to come up, along with Ashwath Jayagopal, the Chief Scientific and Development Officer. I'll kick off questions that we have here. You slightly touched on it during the presentation, but if we could just double-click on what you think is the differentiation on Opus' approach to gene therapy, in particular, the diseases that you mentioned. Yeah. Ben, I'll let you take that since you founded the company. In terms of the differentiation of approach, I think it's a really unique opportunity to take assets that have a very straightforward material set, known capsids, known promoters, very well understood method of delivery. It kind of de-risks our approach as we go into the clinic. I think that we rely on Jean Bennett for her expertise so that we really know the right starting doses to go into. That translational moment from animals to man is a really important moment, and I think just kind of nailing that program after program is a pretty big differentiator for us. Did that answer your question? Yeah. Definitely. I appreciate it. As a quick follow-up to that, I think a lot of the presentation focused on the mechanisms of action and the delivery to the back of the eye. Could you just double-click a bit more on, I guess, more on the safety benefits of that? Just double-clicking on that would be appreciated. Do you want to take that, Ash? Talk a little bit about safety of the product. Sure. To date, the drug products in both BEST1 and LCA5 trials has been well tolerated, with no serious adverse effects. We're not surprised. That's based on a very well-established subretinal delivery technique. We use very low doses of vector compared to approved gene therapies on the market. We have these clinical programs are backed by an extensive non-clinical safety package. This helps to de-risk our approach. Awesome. That's great to hear. Kind of going along the lines of that, with the upcoming milestones that you mentioned and the data readout expected later this year, what readouts are you expecting to be able to talk about with the release later on? Yeah. Well, the one that we would index most people to, the biggest value inflection for the company, will be the BEST1 readout in the mid-year. Our goal for that readout will be to show in the first cohort, a full cohort of data, obviously focused on safety first. Then on target engagement, we think we should be able to show meaningful target engagement. Again, to reiterate the things to look at are, it's really beautiful because we can study this disease at a cellular level in humans using electrophysiology. That should translate to a macro imaging endpoint with OCT, which then should cross over into multiple different types of functional improvement, either with different types of visual acuity or with microperimetry. I'd index to that. I think that's going to be the most important thing for the company this year. Awesome. That's very exciting, and we look forward to it. Briefly moving on to the LCA5 program. Not knowing much about it myself, would love to hear a bit more about what does the therapeutic window look like for a patient with this? Could you talk a bit more about the rate of degeneration and exactly how OPGX, the program, how does it fit into the window that the patients are provided and the options that they have? Yeah, totally. Ash, want to talk about that one? Sure. In LCA5 inherited retinal degenerations, this program was selected as the first in the OPUS portfolio, really because of our conviction and confidence in the treatment potential for gene augmentation. In LCA5, although the visual function declines severely in the first decade of life, most patients are diagnosed as legally blind within those first few years of life. There persists a viable photoreceptor structure that we observe in natural history studies going into the third and fourth decade of life. These patients have poorly functioning photoreceptors, but they are viable, and we believe that they can be restored by a low dose restoration of a ciliary structural protein that they're missing. Early results indicate that it is indeed possible, even in patients in their 30s, to restore what we believe to be clinically meaningful real-world visual function. Hopefully proving out Dr. Bennett's hypothesis. Awesome. Thank you. I appreciate that. Last question before I turn it over to the audience or any closing remarks. I think this is a question all biotech and pharmaceutical companies have. With so many great programs and all the diseases that the team is studying, how is the team thinking about prioritization? Obviously, with the data releases, that makes it a bit easier to do, but would love to hear, given the extensive pipeline the team has. It's a great question and something that is unique to us, but we think a whole lot about, and we think it actually is very interesting for patients and for stakeholders in the company. We pick programs that fundamentally have high probability of success with efficient development pathways. What you're going to see here is manufacturing costs and timelines are reasonable because we're not trying to invent new manufacturing techniques or anything like that. We're doing straightforward AAV augmentation. We're picking diseases where the pathology could be reversed, which allows you to see an improvement, and as we saw in LCA5, as early as a month. We're picking diseases, we're picking manufacturing techniques, we're picking science that really, I think, the first principle way to think about it is this is more of a development company, less of a discovery company. Awesome. Our goal is just to get approved products. We're going as fast and as quickly as we can towards that. Truly the goal. Thank you so much. I'll leave it. Any other questions from the audience or any closing remarks? Oh. Yeah. I have a quick question about the presbyopia asset. Yeah. Is it expected to be a long duration treatment option, like lasts more than eight hours a day or? Yep. One of the unique aspects about this presbyopia asset is that you dose it at night and it lasts for up to 24 hours. The reason that we can do that is because you fundamentally don't have the issue with dimming that you get with some of the other presbyopia assets out there. The reason for that is fundamental biology. Our target pupil diameter is 2.5 mm. The target pupil diameter for the pilocarpine or pilocarpine-like products that are available in the market is more like 1 mm. If you don't dim the patient's vision, then you can dose at night, and you can dose with longer durability. Mm-hmm. It's a great question. Yeah. Yes, ma'am. Yeah. I was just curious about whether you intend to commercialize the approved products when approved, or you focus on being a development company. Just thinking about that. This is a really great question. A couple sort of first principle considerations here. Number one is that in the United States, these are small populations. The call point for a sales team for BEST1, the biggest indication, would be around 2,000 doctors. It's very reasonable you could do this. As opposed to phentolamine, which we partnered with Viatris on, because that is a mass market. The presbyopia market's 140 million Americans or so. They're very different profiles in the United States. You certainly could commercialize this in the United States. The second critical sort of first principle fact here is that these inherited retinal degenerations have different founder effects in different regions of the world. Some of these, for example, LCA5 is very common in Germany, MERTK very common in the Middle East, CNGB1 very common in Asia. I do think that there's a need for a global type commercialization, which is going to be tricky, but it's something that Luxturna has been succeeding with and that we're looking at different avenues for how to do. We see these gene therapies not just as U.S. products, but as global products. We think that you will get reimbursed globally. Fundamentally, back to what I said earlier, if truly these results kind of hold and are replicated in the other programs, then I think that people will want these for their children. Yeah. Good question. Any other questions? All right. If there's no further questions, we'll wrap up the presentation. Thank you so much all for attending, and thank you all for presenting. Appreciate it. If there are any closing remarks, please go ahead. No, just thank you for everybody that came. This is great to see the room. Thank you to J.P. Morgan for the invitation and for all the support.