Opus Genetics, Inc. (IRD) March 25, 2026 Conference Transcript

Well, good morning, everyone. I'm Lisa Walter, biotech analyst at RBC Capital Markets. Thanks for joining us at RBC's ophthalmology conference. This session, we have George McGrath, chief executive officer of Opus Genetics. George, thanks so much for joining us today. How are you doing?

Doing wonderfully. Thank you, Lisa. And thank you to the RBC team for inviting us.

Well, it's a pleasure to host you this morning. George, maybe to kick things off, could you maybe give us a big picture overview of the company and give us an idea about where things stand with your inherited retinal disease programs?

Yeah, totally. I mean, it's a great space to be in right now. A lot of activity in inherited retinal diseases. We have a pipeline of seven gene therapy assets that are all pretty straightforward gene augmentation with the exception of one, which is a knockdown and replace, but, um, but all pretty straightforward meant to be fast and efficient development programs to get these to patients. Um, the technology is mostly out of UPenn, which was, uh, from the lab of Dr. Gene Bennett, who was one of the co-inventors of Luxterna and with, with some technology out of Harvard with Eric Pierce. And so we've got two of them in the clinic now. Um, they're moving fast. The first one is LC5, which is into a pivotal trial. That's the one that was featured on Good Morning America in November. And then the second is Best Disease, which has treated our, we've reported on data for our first patient, and we're going to be reporting in mid-year on the first cohort of patients.

Got it. Thanks for that overview, George. Maybe more broadly, you know, Opus, as you said, you do have a lot of experience developing gene therapies for inherited retinal diseases, and including LCA5, as you mentioned, and the Best One program. Can you tell us why IRDs are attractive areas for clinical development and why you think gene therapies are well positioned to succeed in these diseases?

Yeah, yeah, it's a good question. So every aspect of the program, you know, is picked for a reason. So there's 350 of these genetic defects that can cause childhood blindness. And we've selected the ones where we think we can see an improvement of vision, like a reversal of pathology, as early as three months, in some cases, one month for the first two programs. So we're looking not to slow progression of anything, but we're looking to actually restore vision. And so when you restore vision, you know, really quickly if you have a product or not. So you don't have to wait long periods of time or spend massive amounts of capital to get to know whether or not your target is engaging. The second aspect is that these gene therapies are selected to be de-risked. These, the ones that we're doing are subretinal delivery, AV2s, AV8s, things that have been used before that we we know are well tolerated in the eye. And they're targeting these diseases where the structure of function dissociation structure of photoreceptors is there. It's just not functioning because it's missing one component. So it's not really, you know, it's not really exotic science that we're going after. And the third thing is that these are rare diseases. And in the current FDA environment, you know, it's pretty amenable to small trial sizes. So for example, The Luxterna program, the Pivotal, I think was 27 patients. And so we think that that leads to pretty quick enrollment, pretty quick follow up, and just a capital efficient, you know, fund development program, to be honest. got it got it no that's super helpful um let's maybe talk about the the best one program first uh this recently started in the clinic and george maybe you could just start off start us off with some basics like what is the what is the unmet need and best one and and what is the the prevalence of this disease yeah well the unmet need is huge so so best one disease is a calcium chloride channel that's missing. So from the RPE cells, the RPE is the support layer of cells. It's a monolayer underneath the photoreceptors that's responsible for trafficking the byproducts of the photoreceptors out of the, you know, out of the subretinal space into the circulatory system for disposal. If you're missing the best channel, the best channel is a calcium chloride channel that creates that electrical gradient across the rpe that kind of sucks that fluid out those byproducts out if you're missing that that material backs up under the retina and you end up with a low retinal detachment and with that becomes distortion in vision now over time with the photoreceptors detached right there they will actually atrophy and it'll end up with an area of like geographic atrophy. So in our, in, in the disease, these patients are typically in like their twenties, thirties, forties, as far as age goes. And they, they show up at their doctor's office with mild distortion of their vision due to that fluid under the building up under the retina, under the photoreceptors. And over time that gets a lot worse and they end up going blind over the course of three to five years. So we have a nice therapeutic window to treat. We have a disease that's pretty straightforward to diagnose. For a lot of these patients, you don't even need a genetic test. You can see this egg yolk lesion is sort of the pathognomonic term for it. And there are no other options right now. So we've done some pretty extensive epidemiology work based on the literature and based on genotyped patients, and we come out to a number of around 8,500 or so, maybe 9,000 patients in the U.S. that would be amenable to treatment. That number could be significantly higher, particularly because not all patients are genotyped at time of diagnosis. But we feel like it's a big unnet need. And it's a pretty straightforward pathology. And in the first patient, at least we reported, not only did we reverse the pathology by making that fluid go away under the retina, but the patient's vision significantly improved.

Maybe share a little bit more background on that first patient that you dosed. They did experience some improvement in vision. Can you share some of the efficacy there? I know it's only one patient, but it would be interesting to hear those results. And could you also share a little bit of the detail on safety?

Yeah, definitely. So this was a sentinel patient. So she was very severe. So she was 63 years old. She had the autosomal recessive version of the disease. And she had been symptomatic since she first noticed her vision was going when she got her driver's license when she was 15. she went kind of blind at age 33 and that's when she started using a cane you know to ambulate and started needing you know real low vision type devices and so she had been blind for say 30 years or so um when she was treated um the first thing is that it was safe and well tolerated so she had no intraocular inflammation. She had no treatment-related adverse events. She did do a steroid taper. That's the typical Luxterna taper of oral and topical steroids over a month. And in follow-up out to three months, she had tolerated the treatment very well. What we saw in her objectively on her exam was that she had a pocket of subretinal fluid or or systoid changes in the retina that went away as you know around a month and was gone at three months um that was correlated with a functional improvement in vision and that was the equivalent of 12 letters of vision and at each time point she had more and more so i think it went like four letters nine letters and 12 and that was not seen in the fellow eye obviously um with that 12 what that 12 letters really meant for her was that she went from like being able to see like maybe two fingers if you hold them right here in front of her face to almost being able to see on the eye chart so it was really a dramatic like day-to-day life improvement in her vision from from this got it that that's very uh very interesting results uh and george i apologize i kind of skipped ahead a little bit here but can you maybe just uh give us some background on uh the opgx best one asset uh maybe a little bit more detail the capsid and the transgene yeah totally so it's an av2 um so it's the same capsid as luxterna and it's a full length it's the full best one transgene so it's the full protein um it's a pentamer protein um and then it's got the it's got the best one native promoter and so you've got a couple things that are in your favor from a safety standpoint number one is that you're not using a ubiquitous promoter using a specific promoter for best one so we know that it's going to be expressed in the rp cells and that there should be little off-target expression um because best one's not expressed natively and other cell types. The second thing is the capsid has been de-risked through the Luxterna experience. So from a drug product standpoint, it's a pretty de-risked product, and it's being delivered at a dose that is two log units lower than Luxterna was. So we're delivering it in an E9 dose, which is great. And that has to do with just the stoichiometry of it. The best one is you don't have to express a lot of protein to get a big impact.

Got it. Very, very helpful. And we know you've dosed the sentinel patient. Can you maybe share a little bit more on the phase one to trial design?

And can you remind us when the additional patients can be dosed and when they can move forward? yeah totally um the uh so the uh um so the current trial design is a phase one dose escalation study and there's two doses there's one and a half e9 and there's four and a half e9 each cohort has five patients one sentinel patient then four additional patients so for the data we report at Macula Society that I just told you about, that woman, was a sentinel patient for the low-dose cohort. So mid-year, we'll present her plus the four additional patients to make a complete cohort of five patients, and we'll have three months' data for that. So at the mid-year update, there's going to be an inflection point with this, and this is the same thing we did for the LC5 program. So we're using that kind of as a template. What we'll do is if we see an improvement in the subretinal fluid on OCT in a majority of the patients in the Lotus cohort, to a degree where we think we're reaching the therapeutic maximum, we would go ahead and flip that into a pivotal trial, which would be approximately 30 patients randomized into either a sham or treatment. If you see partial resolution of fluid, but not full resolution, then we may dose escalate, treat an additional five patients, then adapt into the pivotal program. So back to like talking about how efficient the program can be. With LCA5, our first program that's in phase three right now, we treated six patients. Those six patients, all six of them improved. We flipped it immediately into a pivotal without doing additional dose range finding.

George, do you think essentially you could do something similar with best one? Like how quickly, I guess, could you go to a pivotal?

Yeah, totally. Like we think we can do the, we're planning to do the exact same sort of scheme for best one. And so we think that if we show, you know, majority of these patients in the first cohort, improving significantly on OCT, that we'd be starting the pivotal trial like this year.

Do you think given the result with the Sentinel patient that you already have an effective dose?

So for the Sentinel patient, we certainly have, at least with the data we have to date, the data we have to date, which is only three-month data for that patient that we have reached sort of a theoretically maximal improvement for that patient because we've resolved the subrinal fluid that was amenable to treatment. So for that patient, we certainly have an efficacious dose. And if we had, and that patient, I think is the model patient. Like if we see a majority of patients respond like she did, then that's exactly when we would flip it into the pivotal trial.

Got it. Got it. So you're dosing four more patients at this dose level. And is it fair to say if they have as good of an as a result that that would be the dose level that you would move forward with?

Yeah, totally. I mean, she was a home run. So if we can see if we see four additional like that we'll be in a pivotal trial got it got it and george do you think uh bcva gain or bcva change from baseline uh that that would be an approvable endpoint and one that you would uh go forward with in a pivotal study it could be so certainly bcva has for that um the uh the other so so you know bcva is an an easy one when we think about other endpoints um you know from a regulatory standpoint microperimetry also has some precedent at the agency and that one is interesting for best disease because if you'll remember microperimetry you overlay a grid on the retina and you point-wise test the sensitivity light of different spot locations on the retina well you can place that grid sort of directly over where the lesion is in best disease and actually test right there so so microperimetry has certain advantages too now microperimetry is more difficult to do like you have to have better baseline vision so that's why she could not do microperimetry because she was too blind for it too too far gone um but the

other four could so so i think we'll have like you know either best corrective visual acuity microperimetry you know we'll kind of go where the data leads us on the end point and the other four patients being enrolled are they um are they going to be less severe than the sentinel patient Do they have some vision retention?

Yeah, totally. I mean, just like any phase one, the investigators are sort of starting with the most severe, and then they're walking it back kind of incrementally to less severe patients in a very thoughtful way.

Got it. That's helpful. Well, maybe let's talk about the LCA A5 program. Can you maybe remind us of the opportunity here, the prevalence, and what are some of the basics of this inherited retinal disease?

Well, LCA5 is a really interesting disease because the biology is really well known. And so you're missing this protein called libracillin. And when you're missing libracillin, the photoreceptors, instead of being these long kind of, you know, rod-like structures, they kind of accordion down on themselves. And so if you restore the libracillin, the photoreceptors elongate back out. And at that point, they can actually sense light. You know, they can turn light into an electrical potential that goes into your brain. Um, and so the, uh, the gene therapy is delivered via subretinal delivery, very similar to what we talked about with best disease, a little bit different capsid, one that's more, um, trophic towards photoreceptors, but well known nonetheless. And what we did is we treated six patients, three adults, three kids. And all six of those patients had a clinically meaningful response. Now, when I say that, in this disease, we measured a few different things. So visual acuity, we saw a pretty dramatic separation from the other eye in visual acuity that started at the first time point of a month and was persistent out in the longest all the way out to 18 months. FST, full field stimulus threshold testing, this is where you shine a light at the eye and you vary the intensity and you have the patient kind of click a button when they see the light. And so it's measuring just the sensitivity of the light of the eye. We saw, you know, a log improvement in that, logarithmic improvement in that with patients We did a challenge course, like a maze that was, ours was actually done in virtual reality. And the way you do that is you present objects, you know, kind of in the periphery, like a ceiling fan or skateboard on the ground or desk, things like that. And you ask the patient to touch them. And so we saw improvement in the number of objects they could see in the peripheral vision in that test. And then for two of the patients, they had good enough vision where they could do that micropermetry test I talked about earlier. And they had a dramatic, I mean, one patient had an 18-fold improvement in macular sensitivity on the micropermetry. So the unique thing about the LC5 program is that all the endpoints were going in the right direction for essentially all the patients. And so that's a pretty awesome thing to have happen. So we went to the agency, the FDA, it was granted ORMAT status. We flipped it into a pivotal trial, and we're currently enrolling a pivotal that's as few as eight patients. This is an ultra rare. So the incidence is 200 patients in the US or prevalence is 200 patients in the US. And and those eight patients are currently being enrolled. They're going to serve as their own control. So we're following them for six months. Then we're going to treat them. And, you know, you hope that for all the endpoints, you're kind of stable during six months. You treat them and then they improve. So that's that's sort of the LC5 program in a nutshell. all.

George, are these, are you enrolling pediatric and adult patients or how should we think about the right time to capture patients? What's the ideal time to treat them?

We are. Yeah. So, so certainly, I mean, what it comes down to is, is are the, you know, photoreceptor health, right? So if the photoreceptors are present and aren't atrophied, then we think we can intervene. Well, more photoreceptors are present and not atrophied in children than they are adults. And so it follows logically that treating children should give you an accentuated response. And that's exactly what we saw in the three children that we treated. So when we treated the six patients, three were adults, three were adolescents, like teenage years. And those three adolescents had an accentuated response compared to the adults.

So treating them earlier in the disease, they should, in theory, have a better result, a better outcome.

Exactly. Exactly.

And have you shared the phase three trial design? Have you shared what the primary endpoint is going to be?

We haven't yet. We're still talking to the FDA about that. So we'll update the market as soon as we have some clarity on exactly what the primary endpoint will be.

Got it. And you explored, are you leading toward, I guess, what would be your plan for my mission?

Yeah, my primary had the biggest magnitude change, and so we liked that one for sure. We also liked visual acuity. That one had a really good signal. We also, FST was great, like a logarithmic scale improvement. So we're kind of going through those and a couple others with the ACE as well.

Got it. And does this also have a rare pediatric disease designation?

Yes, it does. So we're very, we're sort of very grateful that the, uh, the prior review voucher program was reinstated earlier this year. Um, so as a matter of fact, this one has been granted rare pediatric, all of our programs should qualify for rare pediatric when they get to the right point in clinical. Uh, would best, best one also qualify for the recessive version would for sure. So the recessive version presents in children. The dominant version presents more in working-edge adults. So the recessive one would qualify.

And are you exploring recessive best-won patients?

Absolutely, yeah. So the first patient we treated was actually a recessive patient. Yeah, so she had been blind since, you know, she had started losing vision as a child, and she was 63. when treated.

Got it. Got it. Understood. Understood. Well, George, I do want to touch on the presbyopia program that's ongoing. I believe there's a PDUFA date upcoming in October, correct?

There is. Yes. So PDUFA is in October. So we're excited about that. We were really excited about the Vega trial results and think that it's really differentiated in the market, you know, so, so it's, it's a good one. We're really happy with our partner at Beatrice and, um, you know, the economics on it are pretty significant for us, a double digit royalty, um, that tears into the twenties. So that, um, as you could imagine, you know, that creates a lot of optionality on, you know, pulling, pulling capital into the company.

Well, presbyopia is a very different opportunity than inherited retinal disease. Can you maybe refresh our memory? What is the opportunity here?

What are we talking about here in terms of prevalence? mm-hmm yeah so it's literally like the opposite like the ird stuff is some of the most rare diseases in ophthalmology and presbyopia is probably one of the most common disease diseases in um in all americans right so it's every american above the age of say 45 or so needs reading glasses that's presbyopia and so the the fundamental value proposition is instead if you don't want to have to wear reading glasses you can use an eyedrop that will give you the ability to keep your distance vision but also be able to see up close without the readers and um and so it's a pretty cool thing um it's it's definitely more mass market and that's why we partnered it with with Beatrice was because Beatrice has the um the scale to be able to reach and penetrate a big indication, whereas we're more focused on, you know, our team is more focused on rare disease.

Got it. So this is, this is like over 100 million patients potentially that have presbyopia that could potentially benefit from, from an eye drop. Is that fair?

That's fair. Correct. Yeah.

Yeah. Yeah. Complete polar opposite from IRDs. That's, that's for sure. Does, does it help that there's been two recent launches in Presbyopia? Viz got approved last year and Ubezi recently got approved in January. Does that help this market?

Yeah, totally. Totally. Like I think, I think it's going to give optionality in the market, right? So I think that like Kulosi and Viz are very powerful drugs, right? They do a really good job of giving you very good up-close vision in bright conditions. Our drop, I think, is going to be positioned more where you can use it in dim light conditions. So we don't expect to have that warning label on the product. But we actually have a phase three trial going and actually helping people with dim light disturbances. And then ours, ours, it works fundamentally different than how Viz or Kulosi do. And therefore, you know, we don't expect to get the warning label for retinal detachments. And so I think I see a world where, you know, our drug will probably be used first as, you know, a safe, good option for day to day use. If you need finer visual acuity in bright light conditions, then it, you know, it, it, you, you might progress on to, to vis or kulosi. So, so it'll be an interesting sort of value proposition for patients. And it's a great thing. I mean, patients are going to, I mean, this time next year, patients are going to have a lot of options for presbyopia.

Certainly. It's certainly it's going to be very different next year. And maybe maybe we won't see eyeglasses anymore. I don't know. I don't know.

That would be awesome.

Is there anything else, any other indications that Opus is thinking of entering next? Are there other inherited retinal diseases that you want to flag?

Yeah, no, I mean, we're going to run right through these seven that we have. And, and we think that these are really meet our sort of first principles, which is that you should see an improvement in vision very early, you should be, they should be pretty straightforward to manufacture, and they should be, you know, pretty efficient to develop in the clinic. And so we like that model a lot. And I don't foresee us, you know, getting into big, massive, long programs like we're going to just keep punching out these things as efficiently as we can.

Got it. And would these be, are you thinking of trying to take more opportunities with pediatric indications that would be PRV eligible? Is that the way to think about things?

Yeah, totally. So, so yeah, so like the seven that we have in our pipeline are all sort of PRV eligible. And so we definitely like that PRV type type model. But at the same time, you know, we're also going after, you know, a row and some programs like that that have big, big numbers of patients and adults as well. And so I think that does, I think there'll be a mix there. It won't be all pediatrics, but it'll be, it'll be really, it's just chasing the science, De-risked simple science that restores vision rapidly. You know, that's, that's sort of what we're after. And I think that's what we have with all seven of the programs in our, in our pipe.

Got it. That, that's helpful. Um, George, maybe, maybe lastly, uh, can you remind us about the, the latest cash position and, uh, what is the, the operational runway here at Opus?

So, so, you know, the pro forma cash, um, as of, uh, you know, end of year with the 20, with the additional financing that we did in January is, is $75 million. And that gets us, um, you know, that gets us, uh, you know, well into 2027. And, you know, we have several levers to pull that could potentially extend that runway without adding additional dilution. And so, you know, we feel like we're pretty well capitalized right now for what we're trying to do.

Got it. Good to know. Well, George, I'm afraid we're out of time. Thanks so much for joining us today. It's really been a pleasure hosting you. uh yeah thank you lisa and thank you to the rbc team well thanks so much everyone for listening in uh that ends the session take care