Opus Genetics, Inc. (IRD) Earnings Call Transcript & Summary

Greetings, and welcome to the Opus Genetics LCA5 Data Conference Call. [Operator Instructions] Please note that the webcast participants will be able to see and hear the video. However, teleconference participants dialed-in by phone will need to view the video in the Event Replay in the Investors section of the company's website. As a reminder, this conference call is being recorded. I will now turn the conference over to your host, Jenny Kobin, Opus Investor Relations. Ma'am, please go ahead.

Good morning, and thank you for joining us today for our call to discuss recent results from the Opus Genetics LCA5 Clinical Development Program. Before we begin, I would like to remind you that during today's call, we will be making certain forward-looking statements. Various remarks that we make during this call about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factors section of our annual report on Form 10-K for the year ended December 31, 2024, our quarterly reports on Form 10-Q for the quarters ended March 31, 2025 and June 30, 2025, and our other SEC filings available on our website. In addition, any forward-looking statements represent our views as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements in the future, we specifically disclaim any obligation to do so even if our views change. Presenting on the call today, we have Dr. George Magrath, Chief Executive Officer; and Dr. Sally Tucker, Senior Vice President of Clinical Development. They will summarize our LCA5 clinical study data. In addition, Dr. Ben Yerxa, President; Dr. Ash Jayagopal, Chief Scientific and Development Officer; and Rob Gagnon, Chief Financial Officer, are with us today and will participate in the Q&A portion of our call. The remarks on today's call will be accompanied by a slide presentation, which is available in the Events section of Opus Genetics Investor Relations website at opusgtx.com. A recording of this call will be available on the website later today. I would now like to turn the call over to Dr. Magrath.

Thank you, Jenny, and thank you all for joining us this morning. We're extremely excited to present the recent results of our LCA5 gene therapy clinical development program targeting Leber congenital amaurosis. Notably, our safety and efficacy data for all 3 pediatric participants is positive with observed improvement at 3 months. We will also provide new data on our adult participants supporting durability out to 18 months. Before I turn the call over to Sally to review the clinical data in detail, I will spend a few minutes providing a snapshot of our gene therapy programs targeting inherited retinal diseases and provide a brief overview of our LC5 program. At Opus Genetics, we are focused on accelerating groundbreaking gene therapies for inherited retinal diseases, drawing on robust preclinical validation from leaders in the gene therapy innovation field. By building a portfolio that spans multiple indications targeting inherited retinal diseases, we believe we are strategically positioned to capture a significant share of a multibillion-dollar market, offering numerous opportunities for approved therapies to address rare genetic eye disorders. We have delivered on several critical milestones this year with additional catalysts anticipated in the fourth quarter, particularly driven by progress in our OPGx-BEST1 program. Our portfolio of assets features AAV-based gene therapies, utilizing validated scientific, clinical and regulatory processes and endpoints. These indications have an established regulatory pathway, and we have received rare pediatric orphan drug and regenerative medicine designations. The advancement of our pipeline has been bolstered by non-dilutive funding from the NIH, FDA and patient advocacy groups. Our lead candidate, OPGx-LCA5 is a Phase I/II trial for Leber's congenital amaurosis, and the trial is co-funded by the FDA. OPGx-BEST1, which targets bestrophinopathies and affects a much larger patient population, has cleared its IND, and we expect to initiate a clinical trial in the fourth quarter with our first data expected in the first quarter of 2026. To put our data in context for you, I'd like to provide a summary background on LCA5 and related outcome measures. Despite recent advances in gene therapy, treatment options for inherited retinal diseases remain limited. More than 350 genes are known to cause IRDs, affecting the vision of over 180,000 individuals in the United States alone. Nearly all IRD patients still lack therapies to slow disease progression or restore sight, with Luxturna as the only FDA-approved gene therapy to treat RPE65 mutations. LCA5 is an ultra-rare disease that affects approximately 200 patients in the U.S. and generally presents in the first year of life. LCA5 was selected as our first clinical program due to the significant unmet medical need, the severe early onset nature of the disease and the preserved retinal structure these participants exhibit throughout the first 3 decades of life. This structure-function disassociation creates a favorable pathobiology for AAV gene replacement and presents an opportunity for gene therapies aimed at partial restoration of visual function, making LCA5 both a strategic and high-impact target as our lead program. OPGx-LCA5 is an AAV8-based gene therapy, designed to restore production of the lebercilin protein in the retina. Lebercilin is a ciliary protein critical for the function of photoreceptors in the eye. And in LCA5 patients, this photoreceptor function is severely impaired due to a lack of functioning lebercilin. OPGx-LCA5 is a onetime treatment administered via subretinal injection, which is a validated surgical delivery method for many ophthalmic therapies. By delivering a functional copy of the gene to the retinal photoreceptors, we aim to enable these cells to regain their role in supporting vision, offering new hope to these individuals affected by the severe disorder. Before I turn the call over to Sally to walk through the data, I want to take a moment to describe the secondary efficacy endpoints we are evaluating. It is important to remember that LCA5 patients have extremely low vision with little-to-no formative vision to be able to see or identify an object. Because of this impairment, the tools used to evaluate improvement are not the same as those used for cited individuals. For our visual acuity and other outcomes, we will measure improvement utilizing a scale known as the logarithm of minimal angle of resolution, or logMAR scale. It assesses the ability of individuals spatial resolution or the ability to see black on white. This is assessed in normal-sighted individuals by asking them to read letters on the chart, but with people with extremely low levels of vision, gratings or patterns are used since their vision is so impaired. LogMAR is used to assess visual acuity in a standardized fashion because it is a logarithmic. It means that equal distances on the scale represent multiplicative changes rather than additive ones. This isn't jumping from 0 to 1. It's an exponential improvement. The Full-Field Stimulus Test, or FST, measures the cone or photoreceptor sensitivity. In the eye, you have cones that have peak sensitivities to different wavelengths of light. This includes cones that are more sensitive to long wavelengths or red light, the red cones, or those that are more sensitive to shorter wavelengths of light, the blue cones. FST uses red and blue light to target these different photoreceptors to determine changes in sensitivity of these photoreceptors. As you may recall, FST was the first endpoint that showcased significance in the Luxturna trials as a marker of retinal sensitivity. The Multiple Luminescence (sic) [ Multi-Luminance ] Orientation and Mobility Test, or MLoMT, is a virtual reality mobility course. It assesses what luminance or brightness the individuals can navigate through the course and measures how many objects they can recognize. This is a very sensitive test that actually requires a lot of perception. Users have to follow arrows that are on the floor to navigate the course, while also looking around to identify objects such as a cover, a ceiling fan, a skateboard and a number of other round objects or orbs, some of which are static and some that move. Microperimetry is a detailed eye tracking assisted visual field test that creates a retinal sensitivity map with the macula, the center part of the retina, by testing a patient's response to light at specific points. Many of the participants in our trial could not conduct this test due to poor visual acuity and nystagmus or abnormal eye movements at screening. I will now turn the call over to Dr. Sally Tucker, who leads our clinical development programs, to walk through the results to date of our LCA5 Phase I/II study.

Thank you, George. I am pleased to walk you through the data today, which will showcase the vision improvements for the participants treated to date with OPGx-LCA5. In today's data presentation, we are going to provide 2 important updates: release of the 3-month pediatric data and the 18-month adult data. To date, we have treated 6 participants, 3 adults and 3 pediatric participants, whose demographics are depicted here. One item I will point to on this slide is the baseline visual acuity. As we go through the data, the baseline vision for these participants is important as we are seeing a pattern develop with some of the efficacy outcomes. Of note, in all cases, the participant's eye with the worst vision was treated. The primary endpoint for our Phase I/II study was safety. OPGx-LCA5 was well tolerated by all the participants treated, including the pediatric cohort at 3 months and the adults who we have followed out to 18 months. No ocular serious adverse events and no dose-limiting toxicities have been observed in any of the treated participants to date. All ocular adverse events were mild and were anticipated, and there were no events related to the study drug itself. One pediatric patient, 01-05, presented with a cataract at screening that worsened at 3 months, which was deemed related to the surgical procedure and not to the drug. On durability and visual acuity outcomes, first, we will provide combined data and then provide the individual pediatric participant data. When you are looking at these charts, the negative logMAR values going up the scale indicate improved visual acuity, while the higher logMAR values indicate worse visual acuity. You can see that visual acuity for the combined adult data was maintained out to 18 months when we look at both the mean change from baseline and the mean intraocular difference. This supports the potential for lasting durable responses from this cohort. For the pediatric cohort, similarly to the adult data, there was improved spatial resolution for these individuals. On average, this was slightly greater in the pediatric cohort when compared to the adult cohort with there being a 0.3 logMAR improvement. This is perhaps indicative of the potential for greater changes being possible when younger, more viable photoreceptor cells are treated. When we look at the pediatric participants individually, it is clear that all 3 saw improvements in vision. I'd like to walk you through the visual acuity data for each participant, along with their personal outcome anecdotes that they shared following treatment with OPGx-LCA5. Participant 01-05 had a baseline visual acuity of 2.2 and at 1 month had an improvement of 0.5 logMAR visual acuity. This was the participant that had a worsening of their cataract observed at the 3-month visit, which could be contributing to a more muted visual acuity response at this time point, albeit they still showed an improvement from baseline in their visual acuity. This participant reported being able to walk and cook without the assistance from others and how treatment has helped them in their writing capabilities. The participant's mother described how their daughter's eyes moved and rotated independently of one another prior to surgery, but that now that they seem to be much more coordinated in their movements. Participant 01-06 had baseline visual acuity of 0.96 and is the pediatric participant who had the best vision at baseline. They had a 0.2 logMAR improvement in visual acuity at 3 months and reported a noticeable difference in their visual brightness between their treated and untreated eyes. Participant 01-07 had a baseline score of 2.3 and following treatment had a 0.7 logMAR improvement in visual acuity at 1 month. This improvement was maintained to the 3-month visit, and I will share the anecdote in just a moment. Now moving on to our data related to FST, MLoMT and microperimetry. As a reminder, FST uses red and blue light to target different photoreceptors to determine changes in sensitivity of these photoreceptors. We are pleased to report that we observed overall improvement in all participants. 5 out of the 6 participants improved in dark-adapted FST and 1 participant improved in light-adapted FST. In the adult participants, these gains have been seen out to 18 months. We are really excited about the FST data observed in the pediatric participants. As you can see, these 3-month results have shown FST improvements in all 3 individuals. These 3 participants had large log scale improvements, which were consistent across them all and overall superior to those seen in the adult participants. This is a true indication of the potential improvement in photoreceptor functionality. These next 2 slides will review the MLoMT data from the virtual reality mobility course. When you are looking at these charts, the X-axis represents 4 different light levels, which go from dimmest to brightest. The 0.02 is the dimmest light level and is equivalent to seen outside on a moonless night. 0.07 is similar to a moonlit night. The 0.22 represents being a normally lit room and 0.47 is the brightest light level, similar to a brightly lit office. The colors of each line represent the time points from baseline, month 1, month 3 and for the adults at months 6, 12 and 18. In looking at the MLoMT data for the adults, all participants identified more objects through 18 months compared to baseline. Participant 01-01 had significant improvements in their functionality as observed using the MLoMT. They went from not being able to see any objects at baseline to being able to see 6 out of the 9 objects at 3 of the lighting levels out to 18 months. This is an impressive reflection of the gains this participant was seeing, which she so eloquently describes in the video we will show you at the close of this presentation. As I mentioned earlier, the baseline visual acuity seems to be an important measure when it comes to results using MLoMT. Participant 01-03 was our first sentinel patient, who had no formative vision at screening. This participant went from being unable to navigate through the course prior to treatment to being able to successfully complete the course following treatment. Another anecdote this participant shared with the study team is that following treatment, they were able to navigate through the work corridors without bumping into colleagues, demonstrating the real-world impact reflected in the ability to navigate through the course post treatment. The last adult participant, 01-04, who like 01-01 had better vision at baseline had similar impressive improvements, but across all luminances. In looking at the MLoMT data for the pediatrics, all participants identified more objects through 3 months compared to baseline. The second participant 01-06 showed gains observed at all of the light levels and had a more similar starting visual acuity to the adult participant 01-04. Participant 01-05 and 01-07 had superior visual acuity in FST gains, though the fact that they had no formative vision at screening translated to more subtle MLoMT scores. However, even a minimal score on the virtual test appears to have a real impact in everyday life. Participant 01-07 was mostly nonvisual prior to treatment, but reported taking a visit to a local zoo following treatment where they were able to recognize an owl for the first time. When considering the level of vision observed at screening, it appears that better vision at screening is correlated to more significant improvements in object recognition in the MLoMT test. This makes sense as the better vision could be indicative of the ability to identify objects because they have had the ability to see these objects in the past and have learned how they look. For example, they know what these objects are and have confidence in tapping them when navigating the course, whereas when vision is non-formative, the focus will be head down to follow the arrows to just get through the course safely. Microperimetry is an assessment to measure foveal sensitivity. Participants 01-04 and 01-06 were able to conduct this test with there being positive results. We were not able to conduct the test on the other 4 participants due to their poor visual acuity and nystagmus at screening. Participant 01-04 had both increased sensitivity and movement of fixation toward the fovea post treatment. Sensitivities were barely detected at baseline, but improved and were then detected over the central area of spared photoreceptors. Further, the fixation area was tighter and shifted towards the center. Interocular differences revealed trends towards improvement with the control eye remaining unchanged. Participant 01-06 had gains in sensitivity by area and degree at just 1 month, and we are excited to see how this progresses over time. In summary, we are encouraged by the results seen in the pediatric participants across multiple endpoints. We saw improvements in visual acuity with initial gains being observed as early as 1 month in all 3 participants. On FST, there was evidence of improvement in all 3 participants with increased sensitivity in treated eyes and measurable photoreceptor function. For MLoMT, improvements from baseline was also observed in all 3 participants out to 3 months. And importantly, OPGx-LCA5 was well tolerated in all 3 pediatric participants with there being no ocular serious adverse events or dose-limiting toxicity. All of the ocular adverse events were mild, anticipated and unrelated to the study drug. Similarly, when we look at the totality of the combined data, on visual acuity, we observed improvement in 5 out of 6 participants with initial gains observed as early as 1 month and duration out to 18 months in the adult participants. On dark-adapted FST, we observed improvement in 5 out of 6 participants. And in all 6 participants, we saw increased sensitivity in the treated eyes and measurable photoreceptor function. On MLoMT, we observed significant improvements in object recognition in participants with formative vision at baseline, which we will continue to monitor over time. That concludes the summary of our results, and I will now pass the call over to George to review our next steps.

Thank you, Sally, for walking us through the data. That was excellent. We're thrilled with our results to date with OPGx-LCA5 in both our 3 adults and 3 pediatric participants. We believe the totality of this data supports the impactful vision restoring potential and durability of our gene therapy. LCA5 was well tolerated in all participants with no ocular serious adverse events. We were pleased to see that our treatment provided data supporting potential biologic activity as early as 1 month and also was observed to be durable out to 18 months in the adult participants. We saw robust biologic activity corroborated through multiple functional outcomes. On visual acuity and FST, the improvement suggests potential enhanced visual perception and clarity. And the improvement we saw in MLoMT translates to a potential improved ability to navigate the environment and perform daily activities, which are critical for these participants. We have benefited from having the FDA as a positive partner as LCA5 has been granted multiple key regulatory and operational milestones. A grant from the FDA Office of Orphan Drug Products is supporting the ongoing Phase I/II trial. We have also secured rare pediatric disease, orphan drug and RMAT designations from the FDA. We are potentially eligible to receive a priority review voucher if our Biologics License Application, or BLA approval is granted and the FDA determines the BLA satisfies the criteria for eligibility for priority review. In parallel with clinical progress, we are advancing our manufacturing capabilities, focusing on scaling up both clinical and commercial production and testing to ensure a sufficient supply of cGMP-compliant material. We expect to review the OPGx-LCA5 results and discuss the path forward in this ultra-rare disease with the FDA in the fourth quarter of 2025. We are also on track to begin enrolling participants in our BEST1 Phase I/II clinical trial in the fourth quarter with initial data anticipated in the first quarter of 2026. In closing, I would like to recognize and thank our team, the clinical investigators and staff at the University of Pennsylvania, who are running the study and especially the 6 participants and their families who made the commitment to be part of this groundbreaking research. As Sally described, it is extremely inspirational to hear the real-life impact that these participants have experienced following their treatment. We have shared quotes from each participant on this slide, and we will close our formal remarks with a video clip from one of our adult participants. Listening to Lindsay's experience helps solidify what we do every day and highlights the impact of OPGx-LCA5. Operator, once the video ends, you can open the call for questions. [Presentation]

We hope you have enjoyed the video. Operator, you may now open the line for questions.

[Operator Instructions] Our first question is coming from Debanjana Chatterjee with JonesTrading.

Congrats. So now that you have the early vision trends at hand, are you still considering MLoMT as the ideal registrational endpoint? Or do you think visual acuity or FST could be a more sensitive measurement? And even if it is MLoMT, are you still considering 0.7 to be the best luminance or perhaps something brighter would be a better way to assess the visual improvements?

Yes, Deb, this is George. Great question, and thank you for that. And before I answer your question, it's just -- it's -- I'm just impressed by how much the team has really done this year. Like this is the third clinical trial we've read out this year. And in these results, we were extremely excited about the visual acuity. We were not expecting to see this dramatic of an improvement in the actual visual acuity we saw. And so kind of obviously, if visual acuity is a great -- is an achievable endpoint for the drug product, then we would prefer to use that because it's the most standard traditional method of measuring functional impact of a treatment on a patient. And so we'll have to discuss this with the FDA. We'll show them all the data, and then come up with the right plan going forward. When we think about MLoMT, to answer your question further on that, I think we need to think with the agency about how do we truly get at the most clinically relevant endpoint on the MLoMT. And we were -- I think we've got multiple paths on that based on this data set. So we're pretty reassured by this. And it's exciting when we look at these endpoints that we have a number of great endpoints to choose from, which is a great problem to have. Thank you, Deb.

And if I may, I have a quick follow-up. So this one patient who had the cataract, had muted response at month 3. I'm wondering for a registrational trial, would you consider having an exclusion criteria for patients who have this kind of predisposition at baseline and if that would give you higher results and potentially like higher doses as well?

Yes, potentially. We're sort of working through that right now internally and with the FDA. And so cataract is certainly a known side effect of all vitrectomy surgery, for any indication, whether it's retinal detachment, epiretinal membranes or subretinal delivery like what we're doing. And so there are some pretty common methodologies in the ophthalmology trial landscape that we can use to hopefully control for fluctuations in visual acuity caused by development of cataract from the surgical procedure.

Our next question is coming from Albert Lowe with Craig-Hallum.

Thanks for sharing the data today. I want to ask a little more about the remaining discussion points for alignment for the pivotal trial. Is it still expected to be the small single-arm study? And I guess it sounds like there's a lot of remaining discussion about endpoints. And I know the FDA recently provided some guidance on approval for ultra-rare genetic diseases. So I was also wondering if this gives you any advantages or changes your approach for LCA5 or any of your other programs?

Yes. Great questions, Albert. You're hitting on exactly what we're spending most of our time thinking about right now, which is with -- the FDA is being wonderful. And with them funding the study and also with the RMAT designation, we enjoy really frequent communication with them. And they set out in the new draft guidance that they want to see safety and they want to see biologic plausibility. And so that's what we're out to achieve. And I'll turn it over to Sally to talk a little bit about how she's thinking about the potential pivotal trial.

Thank you, George. Yes. So we're planning to speak with the FDA about the potential pivotal trial for this. As George says, we're having discussions with the agency of how we can accelerate the clinical development for this product given the ultra rarity of the IRD. And we're looking at a pivotal trial that will focus on the endpoints that we've showcased today. So visual acuity, spatial resolution, FST and MLoMT. Again, looking at the correlation as well between what the patient's vision is at screening and knowing that we'll expect to see more enhanced responses in particular measurements dependent upon what their screening visual acuity is. And we'll be having discussions with the FDA on the number of patients that will have to be part of this pivotal trial as well when we meet with them later this year.

Great. Maybe a follow-up. Actually, I was wondering in some patients, it seems like there's on the multi-luminance mobility test. It seems like there were fewer objects identified in some of the brightest conditions. So this seems a little unexpected. And I was curious if you had any ideas on what may be causing this?

So my theory is that these patients naturally have some photophobia. So these patients really, really have trouble in brightly-lit environments. And so I think that what you see here is in this data set is that these patients with already very low vision have difficulty at the lowest extreme and the highest extreme of brightness. And I also think that, that's not -- and what we care about and sort of what Deb was hitting on with the lower -- with sort of the middle luminances is those are more like daily life type luminances. So it's really -- those are the ones that I think we care about the most.

Our next question is coming from Dev Prasad with Lucid Capital Markets.

Congrats on the data. I have a couple of questions. So the first one is the cataract patient that was linked to the surgery. Just wondering, can you do any refinement to reduce such procedure-related complications? And second is we see adult patients having improvement sustained up to 18 months now. What are your -- how do you envision long-term durability in pediatrics? And any thoughts from CMO that these could -- these early treatments can have more persistent benefits?

Yes, Dev, thank you for the question. So to tackle your first question, the -- so cataract is well known from vitrectomy and there are certain technical procedural things you can do during the procedure that minimize cataract that are pretty standardly done. However, you still will get cataract. So the trick, I think, is really to make sure that we control for that in the trial, right? And so using mechanisms within the clinical trial setting to ensure that there's no confounding of our endpoints based on the development of a procedural and not therapeutically related event. So that's how we're sort of thinking about the cataract. The second part of your question about durability, yes, absolutely. So in the adults, these were adults that had never had formed cortical pathways for vision. And the medical term for that's amblyopia, and that puts a ceiling on the potential benefit that the patients can get because the brain just doesn't form normal visual pathways. As you go earlier and earlier, you have more opportunity for the brain to actually form those pathways. And so as we get younger and younger, we would expect not only the durability, but potentially to have a more -- even more impactful benefit for these patients. And that's, I think, what we've seen by going from the adults into the adolescents. And then as it naturally goes younger and younger, I think we'll continue to see that pattern emerge. It's my hope at least.

Our next question is coming from Matthew Caufield with H.C. Wainwright.

Congrats, George and the team on the encouraging update. It was really great to see. So based on the observed LCA5 success, do you believe there's translatability or level of derisking when you consider the comparable delivery and approach for the forthcoming BEST1 program?

It's a great question, Matt. Yes, absolutely. So it's delivered the same way. A lot of the endpoints are similar, although it is a very different sort of pathology. And we think that it's a -- it just falls right into our sort of platform of going after gene augmentation in these inherited retinal diseases. So the BEST1 program is flying right now. It's going really well, and we're really, really excited about more data coming from that program or initial data come from that program in Q1 of next year.

Excellent. Really great to see the updates today.

Thank you, Matt.

Our next question is coming from Boris Peaker with Titan Partners.

I'd like to add my congratulations on the excellent data and the progress. I guess my first question, I just want to understand, you talked about younger patients deriving more benefit, which I guess could be attributed to cortical pathways and maybe preserved retinal structure. Can you comment maybe out of the 200 or so prevalence that you estimate of LCA5, what fraction of them you think could be eligible for treatment? Or the other way, which fraction you think may be not eligible anymore for whatever reason?

Great question, Boris. So -- yes, so when we think about the 200 patients, that is like a total prevalence. And so the natural incidence each year is only several patients or handfuls of patients. So when you think about it, if you think about it from other IRDs that have had penetration into the market, you would expect that most of these patients would actually get treated because there is nothing else available for them. So even if they are more towards the end stage, they're older in life and they have more -- they have less functioning photoreceptors present, I think they still will go for the treatment. So I think the penetration will still be fairly high. I do think that a lot of these are children. That's when they're diagnosed, and that's when the genetic testing is done. So of the 200 people that are out there in the United States that have been genotyped, a vast majority of those were genotyped within the last 20 years at age 2 or 3 of life. And so as genotyping has become more and more available by the good work at places like the Foundation Fighting Blindness and others, we're finding more and more of these patients younger and younger. So I do think the population skews younger. I think should this treatment prove out to be safe and efficacious and should it garner approval by the FDA, the penetration should be may be very high.

Got it. And maybe my last question on the regulatory front. Do you think there's any parallels we could draw in terms of Luxturna or learn things, extrapolate from Luxturna that may impact kind of your regulatory pivotal path forward?

Well, I think there's a recognition of all stakeholders that more of these things need to get developed. So Luxturna was developed in -- it was approved in 2017, I believe. And since then, nothing else has been able to make it across the finish line. And I think that, that is a function of the requirements of programs. And I think that as all the stakeholders involved become more and more willing to work with the community on what are the right endpoints, what are reasonable trial designs, what are the ways that we can actually get these things to patients? Because as you can see, it obviously is affecting these patients' lives. I mean we've treated 6 patients and 6 patients have had their lives changed by this treatment. And so I mean, the real question that I have is pretty simple. It's like, well, if you've restored meaningful vision in 6 out of 6 patients, I mean, how many more times do you have to repeat that? So I think we're in a unique scenario right now, unique time right now where people are really becoming more and more just first principle logical on this topic of what do we really need to feel secure that these drugs are safe and provide benefit to patients.

Got it. Great. And again, congratulations on the progress.

Thank you, Boris. Good to talk to you.

Our next question is coming from James Molloy with Alliance Global Partners.

I'd like to -- looking at the potential Phase III endpoint, would it be reasonable to think that this would be something that you should direct only at pediatrics going forward given sort of the good anecdotal -- the better anecdotal evidence you saw in the pediatrics than you seem to see in the adult, although there was ample evidence of visual improvement in the adults. And I guess what -- all of this anecdotal is not evidence, but in the small population, you have to do what you can. What does constitute you think, the final defining approvable endpoint?

Yes, it's a good question, Jim. So I think -- the way I think about the final primary endpoint for a pivotal trial is that we have a number of -- so this is taking the second part of your question first. We have a number of endpoints that are all pointing in the right direction, whether it's visual acuity, FST, MLoMT, even microperimetry. We feel pretty strongly that this just needs to be a discussion with the agency. And so that's exactly what we're going to do. I think any of those is a clinically meaningful type endpoint that could be used for an approval. And we'll just have to see, right? It will have to be a discussion amongst the company and the agency to see what is the most realistic endpoint to use in an ultra-rare program like this. The answer to your first part of your question, Jim, is, yes, for pediatrics to a degree, right? So I think Boris in part of his comments mentioned that not only cortical plasticity, but structure of the retina is important. So cortical plasticity or the ability of the -- to get to these patients before they become amblyopic is certainly a function of age. And so for that, you need to treat younger. But the presence of photoreceptors, what we've shown on the FST data is when you restore lebercilin into the photoreceptors, you get -- you really do get improved sensitivity of those photoreceptors to light. And so what we're after are people who have present photoreceptors. And so in addition to age that you mentioned, that's what we care about are patients that have photoreceptors that we can potentially modify. And sometimes that persists into the second, third decade of life. And I think that's the improvement that was such a surprise in the adults was that they were able to regain such vision with limited photoreceptors remaining. Good question, Jim.

First time for everything, right? But we're looking at Phase III then what would be the ideal for a trial then? Would it be the same as this trial, same size? Or do you think you need some more? Again, no need to going up again the restriction in fact, it's only 200 of these people in the U.S.

Yes. Yes, Jim. Yes, I think the ideal trial would be use visual acuity as an endpoint and treat enough patients where we feel comfortable we're showing a meaningful difference.

Would it be enough?

I don't have that for you yet. Let me come back to you on that with the -- after we've discussed it with the agency.

Our next question is coming from Madison El-Saadi with B. Riley Securities.

I was just wondering if any of the variability could perhaps be related to the surgery procedure and if there's any, I guess, procedural optimization work that needs to happen on that front? And then are there any medical conferences upcoming you plan to present some of this data?

Totally. Yes. So medical conference is upcoming for the data. We'll announce those as they get accepted. But yes, it's going to be presented likely at multiple conferences over the next 6 months or so. The adult data is actually -- was published in Molecular Therapies in the October issue and will be the cover of that journal for October. So you'll be able to see our patient on the front page of molecular therapy. Pediatric data will come out in conferences, and then we'll publish that in due time. So that's the conference question. And then Madison, remind me the rest of your question, the other part of it?

I asked about the surgery procedure and [indiscernible] variability.

Totally, totally, yes. So it's becoming -- so one of the great things with this is that Luxturna has really paved the way. There probably are 50 or so surgeons in the United States, who are pretty well versed at doing this procedure. It's a -- technically, it's pretty well refined at this point. I will say that this is like the most precise of precision medicine, right? You're delivering these vectors directly to the photoreceptors. I mean I don't -- I'm not aware of anywhere else in medicine where you really can get this targeted to -- on a cellular level with minimal off-target effect, right? There's very minimal systemic exposure to these gene therapies, very minimal exposure and really even in the rest of the eye to these gene therapies. And so this is really, really precise stuff that there's some really amazingly talented surgeons that are doing. And we're obviously going to continue to be very involved as we as we -- as each patient is treated to make sure it's as optimized as possible. I think that goes back to one of the sort of final points that we have, which is that we got a team that's really executing. We've read out 2 Phase IIIs. Now we've read out this ultra-rare study. We've got the BEST1 study that's rolling. I mean the team -- for a small company, the team is really executing well. There's a lot of activity and a lot going on. The sNDA for presbyopia is going to happen this year, just tons of milestones, and a huge congratulations not only to the investigators and everyone else, but the team, too, for pulling it off.

Got it. Understood. And maybe if I could squeeze one more in. You spoke of pediatrics having perhaps more intact circuitry. And obviously, there's a higher level of neuroplasticity one presumes with younger patients. Do you expect that can drive separation within, say, a 12-month time frame? Or is that something that would kind of drive separation years down the road? And do you have a sense of what that delta would need to be that the FDA is kind of looking for in the pediatric cohort?

No, it's a good question. Well, I think the delta that we're seeing is -- I can't speak for the FDA. I don't know yet. We'll have to go talk to them. But certainly, the effect that we're seeing even at 3 months and in the adults at 3 months and then out to 18 months is indicative of a dramatic improvement in their quality of life, and it has been safe and therefore, it should meet the criteria for what we would consider a viable product. To further answer your question, though, about the pediatrics, I do think you're going to -- I think it's going to be -- if you compare it back to Luxturna, like when I've seen these patients, they -- it takes a while to really adapt to your new vision, to develop the new vision. And so I do think it's going to take probably years of kind of gradual improvement. But I don't think that's going to be required to be shown prior to approval. I think what we've shown is fairly compelling. Does that answer your question, Madison?

It does. I mean it looks like you have 6 patients who really delivered a material benefit, too. So congratulations to the team on that.

Thanks, Madison.

As we have reached the end of our question-and-answer session, I would like to turn the call back over to Mr. George Magrath for closing remarks.

Sure. Thank you. And I very much appreciate everybody's questions. Q&A is always the most fun part. We are very excited about this data, and we're very excited not only about the data, but the current environment that we're in, where these treatments that appear to be safe and appear to be efficacious are getting prioritized. And so we do think that there is a lot of room to accelerate this program. And I think that's needed to get this kind of life-changing effect to patients in a reasonable time frame. And so our team, as I mentioned earlier, is really performing at a high level and will be going as efficiently as possible to bring this further to patients. And you'll see that we have the FDA meeting coming up in the fourth quarter on this program, and we'll report back to you guys after we have some clarity on that. We've got the BEST1 data coming in Q1. We've got the sNDA for presbyopia coming later this year. We've got the dim light disturbance trial that's ongoing right now and is enrolling really well. And so there's a lot of activity. It's a fun time at Opus. I was joking around with someone the other day that this is really a blast right now because we're in the middle of executing against a lot of really important science. And it, for the most part, seems to all be working. So I very much appreciate everybody's time and attention this morning, and we look forward to continuing to update you guys as we get material updates. And please contact us if you have any questions.

Thank you. Ladies and gentlemen, this does conclude today's conference. As a reminder, you may view a full replay, including the video of today's call in the Investors section of the company's website at opusgtx.com. You may now disconnect your lines, and we thank you for your participation.