On to the next panel. Thanks, everyone. Joined here by Dr. George Magrath, CEO, and Rob Gagnon, CFO of Opus Genetics. Following this morning's KOL session and gene therapy panel, Opus is a natural break. It sits at an interesting intersection, a small molecule eye drop partnered with Viatris, that FDA approved for presbyopia on Friday. Congrats on that. A day ahead of its PDUFA date and a pipeline of inherited retinal disease gene therapies, including its first registrational trial, which begins dosing this quarter. George, Rob, thanks for being here. As I just mentioned, congrats on Friday's FDA approval on phentolamine. You good? Yeah. For presbyopia, your second U.S. approval supported by the VEGA-2 and VEGA-3 phase III trials. If Viatris commercializes in the U.S., then the approval triggers a milestone payment to Opus.
What are Opus' economics in milestones and royalties, and which launch metrics should investors watch? Presbyopia drops have struggled commercially. Why will this one be different?
Yeah, thanks. I'll start with the economics piece, and then George, maybe you want to take the strategic piece on why this one's different. We do earn a $10 million milestone associated with the approval. We would expect that to come in this quarter. It has up to $130 million total milestones over the course of the arrangement, and it has a very attractive royalty rate as well. The royalty starts off, it's undisclosed, starts off sort of lower teens and then quickly scales up to a higher level, but it's a very attractive royalty for us. Those are the economics.
From a strategic standpoint, it's really interesting because it's going to be, well, it is now, the first approved presbyopia drop that does not have a warning label for potential of a retinal detachment. It also doesn't have the same night glare issues that you get or nighttime dimming issues with some of the strong miotics. It does that because it fundamentally does not engage the ciliary body. We have a much cleaner safety profile that allows one to increase the drop and hopefully should provide a good treatment option for patients.
Fantastic. I had another question, but I'll probably move on only because we want to get to the meat of things here. OPGx-LCA5's registrational phase III enrolls just eight patients, each serving as their own control after a six-month run-in with both eyes treated. Dosing starts this quarter with top-line data by end of 2027. What exactly did FDA agree to on endpoints and statistics, and how many addressable LCA5 patients are there?
Yeah, so good questions. In the pivotal trial, it's an eight-patient pivotal, so I think it's the smallest trial in ophthalmology that's being done for a pivotal. The primary endpoint is going to be proportion of patients that achieve a greater than 7 dB improvement on microperimetry. Now, in the central 16. Microperimetry is a test where you pointwise test the sensitivity of the retina. You have a grid across the retina that tests 68 points or so. The central 16 tests the center, just like it says, the center 16. The average of those needs to be above 7 dB. Now, in our prior study, our average was 10 .5 dB , and so we feel pretty confident in that bar. So right now, the way the trial is structured is that the control for the trial is actually the six-month period preceding treatment.
The patients serve as their own control. The patients have all completed that six-month period, and we're currently dosing. Dosing should conclude pretty quickly here with a readout by the end of next year.
Then—
—addressable market. Yeah. Sorry about that.
No, no.
This is an addressable market of around 150 - 200 patients. Almost all of those are seen at the University of Pennsylvania, and so the commercial efforts will be quite modest as far as what's required to get to those patients. We would expect a pretty high penetration into this population, given the safety profile of the drug and the pretty dramatic efficacy that we've seen for our patients. The fact that most of these patients are captured at the University of Pennsylvania. It will qualify for a priority review voucher as well, so you can see that the economics can be quite meaningful.
Yeah. I think the last one. Definitely sizable there. Okay. Last month, you reported low-dose Cohort 1 data from OPGx-BEST1. All five participants had a clinically meaningful improvement on at least one visual function measure, structural improvement in four or five, and no serious adverse events. You said FDA's aligned on pivotal endpoints with a phase III to start in 2027. What is the plan for Cohort 2 at the higher dose, and how do you pick one for a pivotal dose?
Well, I mean, BEST1, I have been involved with over 100 ophthalmic trials. It is probably the most exciting trial I have been involved with. The fact that the vitelliform material of BEST vitelliform macular dystrophy is disappearing and the function of the retina in exactly the same location is improving is quite a meaningful sort of structure-functional correlation. The second reason it is exciting is to enroll Cohort 1 took us maybe six months. Cohort 2 was five patients. We over-enrolled it to 11 patients in about three weeks. To see that kind of excitement from patients and physicians is, I think, a really cool thing. We have currently enrolled Cohort 2, 11 patients, originally planned at five. We will read out that data in the second quarter of next year, along with an update of potentially flipping into the pivotal trial.
The way we construct these trials is really an adaptive trial. The protocol that we are using for the current dose escalation would be directly adapted into the pivotal trial, and it really saves a lot of time and money on the execution side. We have already aligned with the FDA on what the endpoint will be. Based on Cohort 1, it will be, again, a microperimetry endpoint for the pivotal.
You will just wait for the Cohort 2 results.
Exactly, yes.
Quick follow-up on this, on BEST1 here. Your new epidemiological work suggests 23,600 symptomatic BEST1 patients in the U.S. How confident are you in that number?
I am very confident in that number.
The reason I am confident is because it coincides with what the KOLs have been independently saying. The genesis around the epidemiology is that we originally did the epidemiology based off of the genetically tested patients, essentially. That came out to be about 8,400. What the KOLs started talking about, three of them in particular that were doing a number of events, is that most of these patients are not genotyped because the physical exam in BEST disease is pathognomonic for the disease. Right? When you see the egg yolk lesion, a lot of times you do not need a genetic test. So we actually, at their recommendation, ran a quantitative analysis of 150 eye care providers that triangulated around 23,600 treatable BEST patients. That really independently validated what the KOLs were saying. Same range what they were saying.
Fantastic. For the BEST1 readout, you frame subretinal fluid on OCT as a key measure with 20% or so reduction as a meaningful and near complete resolution in most patients as a trigger for pivotal expansion. The reported data emphasized the vitelliform material, BVMD, and intraretinal fluid in ARB. Some investors felt the goalpost move. How do you respond?
Yeah. The vitelliform material going away was essentially like getting a motorcycle when you had asked for a bike, right? We initially set the bar at subretinal fluid because subretinal fluid is sort of the lowest common denominator. But it is a sign of atrophy. It is not an FDA approvable endpoint. It really does not have much to do with BEST vitelliform macular dystrophy until very late in the disease. But in these late patients, when we were trying to figure out what is sort of the bare minimum, that was where we came out. The fact that vitelliform material went away and the microperimetry in those spots popped, and the FDA agreed to that as the pivotal endpoint, was way better than we ever expected. Right. It really put a lot of wind behind our sails on this.
The only reason we did not flip it into a pivotal trial immediately was because the CMC was not ready. We will have the drug supply for phase III and commercial available early next year. We advanced to Cohort 2 because we had a lot of demand for the study. Again, 11 patients into a five-patient cohort. We had some time on our hands while the manufacturing team finished up the drug supply. We feel like it just beat expectations more than anything else.
Fantastic. Rob, I am not going to go—
Yeah.
Yeah, just to sit there. Let us talk a little bit about the financial consideration. As of August 3rd, you had about $119 million standing on a fully diluted basis, including 16 million pre-funded warrants and 19.6 million warrants that are now callable. You continue to guide runway into 2029. You have said you do not plan additional equity raises given the potential for several priority review vouchers over the next few years. Walk us through that plan. How do you think about calling the warrants, and how dependent is the funding strategy on PRV?
Yeah. As of the second quarter, we reported $80 million of capital. The warrants, they're associated with the BEST1 Cohort 1 data readout that happened. Those warrants have largely been exercised at this point. That's about $20 million. It's about 20 million warrants. That capital has now come in. We already mentioned phentolamine, that'll provide another $10 million in a milestone this quarter. Then we have a fairly attractive credit facility that provides additional draws over the next couple of years. When you take all of that into consideration, that's how we get to a runway into 2029. That does not include any voucher assumptions. The first voucher opportunity would be LCA5. As mentioned, those have been auctioned for $200 million+ at this point.
We're not factoring that into our plans, but that could be our next fundraising opportunity, which would be a voucher.
Okay, great. I know we got 30 seconds here. We can go a minute or two over. I just wanted to kind of circle back to this question that you have RDH12 entering the clinic this quarter. MERTK, M-E-R-T-K, I'm trying to figure out if one of you guys, in Q1 of 2027 and RHO in the second half of 2027 alongside LCA5 investment. Okay, so lots going on. How do you sequence five programs on this balance sheet, and what gets deprioritized if capital tightens?
Fundamentally, these programs are designed to improve vision. When you do that, improve vision within three to six months. When you do that, you really have an idea of whether or not you get target engagement pretty quickly. Because we have a number of programs that are, and several of them that are blockbuster potential, we have the opportunity to prioritize, and we likely will once we see which one is really taking off. It appears that right now that that's BEST disease. So that's a long way of saying that it's a science-driven approach to how we prioritize. I will say that when you're running short trials and you're running trials that show improvement of vision, you're running on a very lean sort of spend.
Each of these programs, from an IND to a BLA, is about $30 million direct spend for manufacturing and clinical. It's definitely doable, and our budget and our current runway does include taking all five of these forward. Like I said, we're following the science, and once we find science that really works on one of these blockbusters, we run with it.
Fantastic. All right. Thank you, George and Rob. That wraps our ophthalmology block. We'll take a short break and resume. Thank you.
Thank you.
Oh, man.