Opus Genetics, Inc. · NASDAQ:IRD
Opus Genetics — Retina in Rio 2026
25 slides from Opus Genetics's conference presentation, Oct 15, 2026
Slide 1: Prediction of Retinal Sensitivity Changes Following Treatment in BEST Disease
Prediction of Retinal Sensitivity Changes Following Treatment in BEST Disease George Magrath, MD Retina in Rio 2026
Slide 2: BEST1: Group of Inherited Retinal Diseases with No Approved Treatment Options
2 BEST1: Group of Inherited Retinal Diseases with a Range of Onset and Slow Rate of Progression and no Approved Treatment Options Overview & Prevalence Mutations in BEST1 have been associated with at least five clinically distinct retinal degenerative diseases, with onset from childhood to adulthood
Slide 3: BEST1 Disease Biology
BEST1 gene encodes for bestrophin-1, a homopentameric (i.e., 5 identical monomers) Ca2+-activated chloride channel required for RPE maintenance and retinal physiology BEST1 mutations in BVMD disrupt cellular ion and fluid homeostasis resulting in electrophysiological abnormalities, RPE dysfunction,
Slide 4: OPGx-BEST1 Gene Therapy is Designed to Target RPE and Restore Bestrophin Function
Designed to restore retinal ion homeostasis in bestrophinopathies, ameliorating retinal structural and functional deficits BEST1 is targeted using the AAV2 capsid employed in LUXTURNA® and an RPE-specific promoter Most bestrophinopathies exhibit a slow rate of decline and central photoreceptors usua
Slide 5: Participant Demographics: Low-Dose Cohort 1
*ETDRS letters equivalent calculated from logMAR.†Worse eye deemed study eye. ARB, autosomal recessive bestrophinopathy; BEST, bestrophin; BVMD, best vitelliform macular dystrophy; ETDRS, Early Treatment Diabetic Retinopathy Study; RPE, retinal pigment epithelium; VA, visual acuity. Participant Demo
Slide 6: Microperimetry Showed BVMD Improvement in the Treated RPE Transitional Zone
Defining the Transitional Zone Border area surrounding the atrophic lesion with RPE and photoreceptors that are structurally intact but functionally compromised or at risk of imminent atrophic progression Highest potential to be rescued with OPGx-BEST1 Treated RPE Transitional Zone is the area of re
Slide 7: Transition Zone as a Microperimetry Endpoint
Transition Zone as a Microperimetry Endpoint
Slide 8: BVMD lesions have a core that is already scotomatous, and normal retina farther out
BVMD lesions have a core that is already scotomatous, and normal retina farther out Between them sits the transitional border zone: Points that still test normal today, immediately next to degenerating retina This zone is concentrated within the central 5° around the fovea Study objective: Natural h
Slide 9: Transition zone had a significant decline in mean sensitivity over time
No meaningful changes in the whole macula, but transition zone had a significant decline in mean sensitivity over time Annual mean sensitivity rate of change (dB/year), by subset of test points - per-eye regression, N = 23 eyes Mean sensitivity across all 68 points did not decline significantly over
Slide 10: Why this matters for trial design
Why this matters for trial design 1 Whole-macula averages hide real progression Global mean sensitivity across all 68 points was statistically unchanged over 4 years; an averaging artifact, not evidence of a stable retina Averages are misleading; mixes healthy-looking spots with already-damaged spot
Slide 11: Learnings from the Ongoing Phase 1/2 Study of OPGx-BEST1
Learnings from the Ongoing Phase 1/2 Study of OPGx-BEST1
Slide 12: Transition Zone Could be Optimized for Greater Specificity
12 Transition Zone Could be Optimized for Greater Specificity Current Study TTZ loci selected Averages of 3.125 and 3.5 dB What We Learned Averages could have been higher with more selective loci Hyperautofluorescent spots alone would have averaged 4-5 dB Future Study Increase specificity for loci l
Slide 13: Microperimetry Improved within the Transitional Zone and Reduced Vitelliform Lesions
BVMD, best vitelliform macular dystrophy. Baseline Month 1 Month 3 Microperimetry Improved within the Transitional Zone and Translated to Reduction in Vitelliform Lesions 13
Slide 14: Microperimetry Improved in the Transitional Zone and Correlated with Decreased Vitelliform Material
Baseline Month 1 Month 3 Microperimetry Improved in the Transitional Zone and Correlated with Decreased Vitelliform Material Baseline Month 3 14
Slide 15: OCT-derived EZ-to-RPE Thickness as a Structural Endpoint
OCT-derived EZ-to-RPE Thickness as a Structural Endpoint
Slide 16: The Hill of Vision: Volumetric Visual Fields Predict Treatment Effect
Fovea-highest sensitivity (sharpest vision) Blind spot (optic disc) ~15° temporal to fixation Periphery (far edge of vision) Sensitivity Also known as the Island of Vision in a Sea of Blindness Classic 3-D model of the visual field introduced by Harry Traquair in the 1920s Sensitivity peaks at the f
Slide 17: Learnings from the Ongoing Phase 1/2 Study of OPGx-BEST1
Learnings from the Ongoing Phase 1/2 Study of OPGx-BEST1
Slide 18: Analysis 1: Spatial relationship between EZ-to-RPE thickness and retinal sensitivity
18 Analysis 1: Characterization of spatial relationship between EZ-to-RPE thickness and retinal sensitivity Comparison Pearson Spearman Measured microperimetry 0.760 0.784 HOV sensitivity 0.749 0.788 Measured, within-eye (subject-eye centered) 0.760 0.784 HOV, within-eye (subject-eye centered) 0.761
Slide 19: Analysis 2: Evaluation of treatment on EZ-to-RPE thickness
19 Analysis 2: Evaluation of treatment on EZ-to-RPE thickness Treated eyes demonstrated a consistent improvement in EZ-to-RPE thickness, with no change in fellow eyes By Day 90, the treated-minus-fellow difference was positive in all 3 participants despite heterogeneous early (Day 30) responses Larg
Slide 20: Analysis 3: Longitudinal structure-function association over time
HOV revealed a modest, but more consistent positive structure-function relationship compared to microperimetry Longitudinal change was coupled with baseline intermediate EZ-to-RPE thickness Strongest coupling was observed in EZ-to-RPE thickness of 5-20 µm Little coupling seen in low (≤5 µm) or high
Slide 21: OCT Biomarkers and Retinal Sensitivity in BVMD
OCT Biomarkers and Retinal Sensitivity in BVMD BVMD, best vitelliform macular dystrophy; OCT, optical coherence tomography.
Slide 22: Clinical Correlation Between OCT Biomarkers and Retinal Sensitivity in BVMD
22 Clinical Correlation Between OCT Biomarkers and Retinal Sensitivity in BVMD Variable Beta coefficient (dB) Hyperautofluorescent (NIR-FAF pattern)* +7.4 Vitelliform lesion (vs atrophy) +7.6 Mixed lesion (vs atrophy) +6.2 Subretinal fluid lesion (vs atrophy) +4.7 ONL thickness, per µm +0.2 P<0.001
Slide 23: Hyperautofluorescence Correlates with Microperimetry Changes in Participant 102-102
Hyperautofluorescence Correlates with Microperimetry Changes in Participant 102-102 Hyperautofluorescence in treated transitional zone Loci improving Hyperautofluorescence in the treated transitional zone was strongly associated with improvement in mean retinal sensitivity 23
Slide 24: Hyperautofluorescence Correlates with Microperimetry Changes in Participant 101-106
24 Hyperautofluorescence Correlates with Microperim Changes in Participant 101-106 Loci improving Hyperautofluorescence in the treated transitional zone was strongly associated with improvement in mean retinal sensitivity Hyperautofluorescence in treated transitional zone
Slide 25: Application to the Opus Clinical Trials: Path to Pivotal Trial
PH 1/2 - COHORT 2 DESIGN 25 Application to the Opus Clinical Trials Microperimetry loci will be prespecified Target: Treated transitional zone, enriched by: Baseline EZ-RPE thickness Hyperautofluorescence Vitelliform material on OCT Clinical rationale: Earlier stage patients have higher magnitude of