Walter, biotech analyst here at RBC Capital Markets. Thanks for joining us at RBC's 2026 Global Healthcare Conference. This session we have Opus Genetics, and we have the pleasure of hosting Dr. Ben Yerxa, President well for the fireside. Ben, thanks so much for joining us today. How are you doing?
Doing great. Hope you're doing well.
I'm doing fantastic. Well, Ben, maybe for those of us who are not familiar with Opus, can you give us a big picture overview of the company and where things stand with the inherited retinal disease programs?
We're a company focusing on gene therapies for inherited retinal disease. We're co-founded by Dr. Jean Bennett, who you may know from, she co-founded Spark, inventor of LUXTURNA. We've been able to put seven assets into our portfolio. Two are in the clinic. The next three will be in the clinic in the next 12 months. We're really busy putting these into the clinic kinda one by one and creating a really nice stream of data coming out of the company.
Got it. Well, I do have a big picture question to ask you, given the current regulatory environment is experiencing a bit of volatility with the departure of Commissioner Marty Makary .
Yeah
I know it's still relatively early and the dust hasn't settled, has there been any impact to any of your programs, particularly for BEST1 or LCA5?
I think right now in terms of like the boots on the ground, the people we meet with at the project level, it's not a huge difference. I think the bigger impact, besides the commissioners, there's no head of CBER right now. There's only an acting head. That's probably a little bit more disruptive than the actual head of the FDA because that's a little bit closer to what we do. I think what we're finding is that new policies they're setting at the top are kind of trickling down to the project team levels. It takes a little bit of time to get there, but it's been pretty good. I mean, for rare disease and gene therapy in our space, it's been pretty steady and pretty favorable for us.
You're mainly dealing with the ophthalmology division of the FDA, correct?
Yes. In CBER, they can have ophthalmologists within CBER. CDER has an ophthalmology division for all their small molecule stuff. Sometimes there's a medical reviewer on the biologic side, but they'll consult with the ophthalmology division. It's a little bit of crosstalk.
Got it. Well, maybe, Ben, before we dive into the individual programs, can we get a little bit more background on the Opus gene therapy platform?
Yeah. We, as I mentioned, we started the company based on conversations with Jean Bennett. Starting with a couple assets at Penn that were just really, really good starts for us because Jean taught us something called structure-function dissociation. It's this concept that the best prospects in our field are the ones where there's a broken function, but the structure remains good for a while. Like the target tissue is still viable for rescue. We kind of accumulated assets based on really high science, structure-function dissociation, and the ability to see quick wins in the clinic. That was kind of the way we got started. We generally try to avoid risk on risk. We use known capsids, known promoters, AAV2, 5, 8 and 9, for example. We know how to make them.
The agency's comfortable with them. No science projects. It's all just like development work.
Well understood capsids going after diseases where the tissues are intact and you could potentially have some impact.
Perfect. Exactly.
Got it. Well, I do wanna flag the R&D day that you are planning to have on June 16th. What should we expect to learn at the R&D Day?
Yes, we realize that we've got three new programs that are gonna be in the clinic in the next 12 months that most people haven't really heard about or had the time to pay attention to them. We wanna kinda set the table up with the science next month so that as we start getting things into the clinic starting later this year and into early next year, the people are a little bit more familiar with these programs 'cause they all stand on their own, on their own scientific merits, and they're all equally exciting.
Got it. Well, we'll touch on those in a second.
Okay.
I have a feeling I know which ones you're talking about. You know, Ben, Opus has a lot of experience with gene therapies for inherited retinal disease. That's kind of the core of the business, if you will. Can you tell us why inherited retinal diseases are attractive areas for clinical development, and why gene therapies are so well-positioned to potentially have success here?
I think in our space, when you're thinking about gene therapies, these are subretinal injections, so it's a tiny dose. It goes exactly into the target tissue. You know exactly how much you've delivered it and where it went, and you have a window into the eye literally where you can see what happens afterwards. It's a really unique situation where very small dose in a compartment within a compartment, no systemic exposure. It really limits potential adverse events on the safety side. On the CMC side, which is half of the drill in gene therapy, we need very small batches. It's not like a scale-up problem on the CMC side. We got a lot going for us in terms of just small dose, small batches, and we can see what happens after we deliver it.
Got it. Well, maybe let's talk about BEST1. This recently completed enrollment in your cohort 1 of your phase I/II study. First of all, can you remind us of the unmet need in BEST1 and maybe what the prevalence is in the U.S.?
Yeah. In BEST1, we estimate about 8,400 patients in the U.S. Now there's a recessive and a dominant form. The recessive is pretty rare. It's one in a million, think about 300, 350 patients in the U.S. The rest are this dominant form. Now, the recessive form is earlier onset, more severe. These patients are diagnosed in their first probably one to two decades of life. They're probably legally blind by the time they're in their 30s. They kind of go atrophic, like they start losing structure as they get into their 30s, 40s, 50s. The dominant form, which is the vast majority of patients, usually notice something in like their 20s, like, or maybe even during a driver's test, like some wavy lines or something like that.
They may go to their doctor and say, "Hey, I need to get an update on my glasses." They'll look in the back of their eye, and they'll see something that looks like an egg yolk. Like, oh my God, you have Best disease. It's pathognomonic for that. If you see an egg yolk in the back of the eye, then they know they got a problem. Even though this patient may be 20/20 or 20/30, they're gonna go blind in the middle of their eye eventually. It's a matter of time. It's kind of insidious because there's no treatment right now. We're the only company working on a trial. Think about like the center of your eye just becoming black. That's what happens over time.
That sounds very upsetting.
Yeah.
You know, you mentioned that these patients, they're heading towards blindness in their thirties. Maybe they're starting to notice symptoms in their twenties. When is the best time to treat these patients with a gene therapy?
We're thinking that, you know, you're not gonna probably treat someone with 20/20 vision, right? There's gonna be some loss of vision before it's gonna justify, you know, a gene therapy. I think, we're starting with patients that are more like 20/100 and then kind of walking to healthier patients, 20/80, 20/60. I think once we establish really good safety, if we can get there and show that the therapy works, we can go younger and younger because we know it's a matter of time. If they've got better structure, it could be an overall better therapy. We'll get there slowly, but I think that, getting into I guess what we call stage two, is probably gonna be a sweet spot eventually.
Got it. Well, let's talk about OPGx-BEST1. This is your gene therapy that you have in development for the disease. Can you share some background on what is the transgene you're delivering, what capsid you're using, the route of administration?
Yep. It's a AAV2 capsid. The gene fits perfectly in the capsid, so no issue there. It's the native promoter of VMD2. We're going in with doses around 1.5E9, so that's 100 times lower than Luxturna. Again, same capsid as Luxturna, same target tissue. We go subretinal injection, so we essentially put the vector right on top of the RPE, which is our target. I think one of the reasons why we can use a lower dose is because we don't need a lot of expression. It's not a highly expressed protein, so think of it as like a little bit goes a long way.
Is it a membrane protein, an enzyme?
Yeah, it's a calcium-activated chloride channel, so membrane-bound on the basolateral side.
Got it. You have the BEST1, phase I/II study that's ongoing. Can you share a little bit more on the trial design? You have a low dose and potentially a high dose. I guess, what do you need to see before proceeding with the high dose? First, can you give us a little background on the trial design, and what are the mechanics for you to proceed from the low to the high dose?
Yeah. BEST1 is designed as a basket trial. We know there are two types of Best disease with the recessive and dominant, we can do a basket where we can enroll both recessive and dominant in the trial. It's five patients per cohort, contemplated two dose levels, it'd be 10 patients total. Typically how we do it is we do a sentinel patient for safety, we wait 30 days, have a DSMB meeting, once we clear safety, we can enroll the rest in parallel. That's how we proceed. We've guided that we'll have data on the first three months for the first five patients in September, for the first cohort. We have to decide whether we're either gonna dose escalate or move into the pivotal portion of the trial.
There's a possibility that the low dose is enough, and you would move that to a pivotal study.
That's possible, yeah. I think it's gonna be data-driven, of course. If we see a majority of patients with a clear improvement in structure and function, think of it as like 20%-30% reduction in the fluid that's classic for BVMD and an improvement in some function like either visual acuity or microperimetry, then we'll know we have very clear target engagement. If the safety is clean, we may just wanna proceed into phase III and not take a risk on an adverse event.
Got it. Well, you do have some data from at least one patient, the sentinel patient. Can you share some background, you know, maybe were the baseline characteristics of this patient? Obviously, they were given the low dose-
Yeah. Yeah.
As that's what you're starting with. Let's start with some background on the patient, then we can talk about the data.
Yep. The sentinel patient was 63 years old. She'd been legally blind since her early thirties, and in fact, relayed to us that she had noticed first fluctuations in her vision when she was doing the driver's test. She still passed the test, but had some issues, you know, in trying to pass those visual tests. Pretty severe patient, you know, classic for a sentinel patient. We're really looking for safety. She had a central pocket of fluid with some viable target tissue underneath that was in the center, in the macula. But also had a fibrotic scar around the center of her eye that, you know, it was kinda gets glued to the bottom of the retina, so it doesn't get treated.
Because she had some viable tissue to be treated, it was a good sentinel patient because there was prospective benefit. Starting vision was counting fingers, so all she could see is do this, like, right in front of her face.
Okay.
Yeah, pretty bad.
Both of her eyes were affected, correct?
Yes. The study eye is usually the worst eye.
Got it.
Yeah.
This sentinel patient that you dosed, they had some pretty impressive BCVA gains, 12 letters of-
Yeah.
Versus baseline, if I have that correct. Were you surprised to see such a large gain, especially in a patient, you know, who was older and had been suffering from this disease for many, many years? Was this a surprising result?
Yeah, I think we were a little surprised. You know, we go into these trials, especially in sentinel patients, really with the expectation of establishing safety. When you see frank efficacy in a sentinel patient, it's always, you know, it's exciting. Once we really dug into the data, I think we understood why we were seeing it. 'Cause basically, that pocket of fluid I told you about was near the macula, and it's pretty well known that if you've got a pocket of fluid in the center of the eye and you get rid of the fluid, vision usually improves. It was a small area, but it happened to be central, which is right where your central acuity comes from. To see a couple lines improvement corresponding to that reduction in fluid, makes us believe it's real.
Typically, you know, three lines of vision is the standard by the FDA for sort of an approvable endpoint. When you go from counting fingers to reading the big E on the eye chart, talk to the patient. It is super meaningful.
Got it. You know, you dosed four out of five patients in cohort-
Yeah.
one, correct? What are your expectations for the rest of this cohort? Are you thinking that they're also going to have a similar double-digit BCVA gain? Because the additional patients, they're a bit younger, right?
Yeah. The cohort's filled out with two recessive and three BVMD. If you look at the baseline characteristics, the dominant patients have much better starting vision at baseline. They're like 20/100 down to like 20/60, I think. There's gonna be a little bit of a ceiling effect on BCVA in terms of gaining three lines for the patients with better vision. We're also looking at low luminance visual acuity, which is like doing the same eye chart, but through a graying filter that makes it darker and harder. That gives us more dynamic range to look for three lines. That'll be interesting. Trying to think of what else I can tell you. The BVMD patients, it's pretty classic. This is kind of what you see in the wild.
You know, they've got a clear pocket of fluid. It goes beyond the central subfield, by the way. A classic egg yolk lesion where you put the microperimetry over that, and you can see that geography of the impaired retinal sensitivity right over that lesion. It's really cool to see.
Well, I know the data is coming in September.
Yep.
Just maybe two questions on BEST1. What are you planning to share in terms of the data in September, and how are you thinking of a primary endpoint for a pivotal study?
Yeah. The data will be pretty rich. It'll be richer than, say, the sentinel patient, 'cause these patients could do other endpoints that the sentinel patient couldn't do. In terms of function, we'll have best-corrected visual acuity, low luminance visual acuity, microperimetry, and also contrast sensitivity. The last one's a little bit more exploratory, but still pretty interesting. The OCTs, there are gonna be a lot of different ways to look at the OCT. In fact, the most important is probably gonna be a volumetric analysis of the fluid. If you just look at the central subfield, it may miss fluid that's outside that central ring. We're gonna look at the total fluid volume and calculate that basically like in nanoliters or microliters. You can also look at the EZ area.
There's another endpoint in the IRD field where you can actually quantify the existence of photoreceptors in a thin layer of the retina. When it's elevated off, you can't see the EZ area 'cause the photoreceptors are kinda flapping. If they kinda sit back down and reestablish that reflective area, we could see a bump in EZ area.
Do any of those stand out to you right now as a potential primary?
A bunch of them can be primary, right? BCVA, of course, LLVA can be. Microperimetry might be one of the more crisp ones here because there's a very low standard deviation. If we see frank improvements in microperimetry right over the pathology, that could be a good one just because the variability is much lower. The OCT stuff could be pretty cool with the FDA. If we clear the pathology like we saw in the dogs, I mean, we've seen them approve things for GA where there was just barely changing, you know, growth of a lesion. If we take it in reverse, I think we'd have a strong argument for that as a standalone endpoint as well.
Got it. Super helpful. Well, maybe let's touch on LCA5.
You know, can you first remind us of the opportunity here, and what did your phase I/II data show that convinced you to move forward with the pivotal study?
Yeah. In LCA5, these kids are pretty much blind at birth, you know, certainly the first one to two years of life. In fact, they often never have any form vision. Their eyes wiggle with nystagmus, like they can't actually focus on anything. As I mentioned before, their structure remains pretty good until their twenties and thirties. I'll give you an example of our first patient. Our sentinel patient was 26 years old, had hand motion vision at baseline, and 30 days after treatment, he could read the big E on eye chart. Surprised the PI. The PI's like, "No way." Actually, he didn't know what an E was because he was a braille reader.
He's like, "Yeah, I can see that." I'm like, "What letter is it?" He's like, "I don't know, I read braille." We started to see results like that in the adults and then in the adolescent patients. We actually went to the FDA with three adult patients of data and got RMAT status, which allows to have more frequent dynamic conversations with the FDA. The adolescent data came in, and we started talking to them about, you know, can we just adapt our trial into a phase III? We literally went from a phase I/II to a fully adaptable phase I, II, III continuous trial, which is great. Like, I've never been able to do that in my life as a drug developer.
They offer that flexibility because they could see the efficacy, and they know these kids are profoundly blind. LCA5 is just it's really exciting. We've got RDEP status, which I think we're the second company to ever get that status. No one really knows exactly what it means except that, we have another shot to talk about, you know, a really creative way to get to a BLA.
Yeah. Our RDEP is relatively a new program.
Yeah.
Started by the FDA, just last September, right?
Yeah. It applies only to populations less than 1,000. Clearly LCA5 with about 170 fits in that bucket.
Got it. The LCA5, the phase III is already enrolling a run-in period, correct?
Right. That's we talked to the FDA about, not just adapting to a phase III, but it's such a small population that you can't do a large controlled trial in a, in a traditional sense. We said, how about each patient is their own control, which we've seen in other gene therapy trials. We're doing a six-month run in natural history to get a really long baseline on these patients, so that after dosing, if we see a complete change in their disease trajectory, we know we've got something there. That's already been agreed to. As we're waiting for final word on the FDA, on the final pivotal endpoint and statistical analysis, we're already getting these patients sort of in the bag so that we're ready to dose them in the second half of this year.
Maybe just, two last questions on LCA5. Are you enrolling both pediatric and adult patients in the phase III?
Yeah.
Yes.
Yeah.
Given the pediatric patients are being enrolled, could this program be eligible for a priority review voucher?
Yeah, we believe so for sure. It's clearly a pediatric disease. We've got Orphan Drug and Rare Pediatric Disease designations already.
Got it. Well, I do wanna touch on your pipeline programs.
RDH12, MERTK, and RHO. You know, these are three additional programs, also rare inherited retinal disease programs. As you mentioned earlier, they're on the cusp of entering the clinic.
Can you maybe remind us what the opportunity here is with these programs? You know, given the learnings from BEST1 and LCA5, do you already have an idea of where to start these at an effective dose with gene therapy?
Yeah. Each one of these is a little different. You know, every IRD has its own unique biology. RDH12 will be the first one in the clinic. It's the second one that came from Jean Bennett's lab. It's an enzyme in the visual cycle, so it's kind of similar to RPE65, except the target tissue is a photoreceptor, so we use an AAV8 capsid. We've got animal data, tox data. You know, we're really ready to get started later this year dosing. Since it's an AAV8 capsid similar to LCA5, we kind of know where to start, frankly. We know what doses are effective in transducing these cells, so we feel pretty good in the way we model our starting doses. That'll be the first one in the clinic.
MERTK is an AAV2 capsid, so it's an RPE target. That trial is going to be done in Abu Dhabi, believe it or not. MERTK is the number three cause of genetic blindness in the Middle East. They have a lot of patients there, and there's a Cleveland Clinic, and they've got a great surgeon, and they've done a lot of LUXTURNA patients with success. We discussed with the Department of Health there about a grant to actually fund the trial. We're excited to be partnering with them because they've got the patients and because of funding the trial. The third one is RHO. RHO, this is a fascinating one. It's a pretty big population. It's about 8,000 patients in the U.S. This is going after retinitis pigmentosa associated with the RHO gene.
It's knocked down and replaced. It's a dominant disease, it's kind of a dual construct. This is gonna be ready to go, start dosing probably first half of next year.
Got it. Ben, are these programs targeting pediatrics or adults? Do we have an idea about when is best to treat these patients?
Yeah. RDH12 and MERTK are clearly pediatric. RHO is more adult onset, but we understand there are some variations where there's early onset. It's mostly an adult disease for RHO.
Could all three of these programs perhaps be eligible for a Priority Review Voucher or maybe just RDH12 and MERTK?
I'd say two out of three for sure, and maybe RHO.
That might be like $400 million non-dilutive capital?
I know. We have easily five out of seven programs are Pediatric Voucher eligible.
Okay. Okay. That's quite a few. Maybe just in the last minute or so here, you also have a presbyopia program that's partnered. You have a PDUFA date upcoming for that in October. I guess, what is the opportunity here for you in presbyopia?
We really see this as a financial asset. It's partnered with Viatris. They've got a large sales force. We get a regulatory milestone on approval. We get a double-digit royalty that tiers into the 20s and some additional regulatory and sales milestones, I think upwards of like $100 million remaining. For us, we just have to complete the development. They kinda do the rest from there. You know, we're waiting to see where the presbyopia market goes, watching LENZ and other people in the space, to see what happens with this.
Got it. Well, maybe just the last question. Can you just remind us about the cash position and what the runway is for Opus?
Yep. We've got $90 million in cash, runway into 2029. That, you know, that could get us to our first PRV auction.
Got it. Well, Ben, it's been a pleasure hosting you today.
Thank you.
Thank you so much for joining us at our healthcare conference.
Thanks for having me.