Slide 1: Delivering on the Promise of Gene Therapy for Rare Inherited Retinal Diseases
Delivering on the Promise of Gene Therapy for Rare Inherited Retinal Diseases October 2026 Kendall, RDH12 patient, with Maya
Slide 2: Disclosures and Forward-Looking Statements
Disclosures and Forward-Looking Statements This presentation contains forward-looking statements. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “aim,” “may,” “ongoing,” “plan,” “potenti
Slide 3: The Opus Opportunity: Fully-Funded to Advance 5 IRD Clinical Programs
The Opus Opportunity: Fully-Funded to Advance 5 IRD Clinical Programs 7 Targeted IRD AAV gene therapy assets Validated science & delivery approach 1 multiple indications st Mover advantage in Portfolio approach produces multiple Follow-on treatments from the first Broad IP protection and eligible fo
Slide 4: Precision-Targeted, One-Time-Treatment for Rare Diseases
Precision-Targeted, One-Time-Treatment for Rare Diseases 350+ genes known to cause IRDs • World-class science from pioneers in gene therapy Proven subretinal delivery with established • Structure-function biology well-characterized with safety profile and clinical precedent measurable outcomes amena
Slide 5: Structure-Function Dissociation: The Clinical Imperative
Structure-Function Dissociation: The Clinical Imperative Targeting Diseases Where the Structure Is Intact Retinal structure is relatively preserved even though visual function is already impaired This creates a “therapeutic window” where there are still enough viable cells for AAV gene replacement t
Slide 6: Building a Differentiated Gene Therapy Platform
Building a Differentiated Gene Therapy Platform Building a Differentiated Gene Therapy Platform Preclinical IND-enabling Phase 1/2 Phase 3 Approval OPGx-LCA5 LCA co-funded by FDA OOPD OPGx-BEST1 Bestrophinopathies OPGx-RDH12 LCA co-funded by Global RDH12 Alliance OPGx-MERTK RP co-funded by FFB RD Fu
Slide 7: IRD Patient Prevalence Across Select Global Markets Provides Significant Opportunity
IRD Patient Prevalence Across Select Global Markets Provides Significant Opportunity Total Middle EU4 + Middle East/ United EU4 China Gene U.S. China Prevalence East/ UK North Africa States + UK by Gene North Africa 39,600 40,970 12,880 45,200 LCA5 ~170 ~170 ~1,400 ~1,500 ~3,240 BEST1* ~23,600 ~4,90
Slide 8: Multiple Anticipated Clinical Inflection Points Through 2027
Multiple Anticpated Clinical Inflection Points Through 2027 2027 Current cash runway extends into 2029 BEST1 Pivotal and is expected to fund five clinical programs Q2 2027 Study Start through multiple critical inflection points BEST1 Cohort 2 Q1 2027 results MERTK clinical study initiation Q4 2026 R
Slide 9: OPGx-BEST1
OPGx-BEST1 Juan, BEST1 patient
Slide 10: BEST1: Group of Inherited Retinal Diseases with No Approved Treatment Options
BEST1: Group of Inherited Retinal Diseases with a Range of Onset and Slow Rate of Progression and no Approved Treatment Options • Mutations in BEST1 have been associated with at least five clinically distinct retinal degenerative diseases, with onset from childhood to Overview & adulthood1 Most Comm
Slide 11: BEST1 Disease Biology
Photoreceptors S T AG E 1 Pre-vitelliform Retinal Pigment BEST1 Disease Biology VITELLIFORM DEPOSITS Epithelium Bruch’s Membrane Choriocapillaris • BEST1 gene encodes for bestrophin-1, a homopentameric VITELLIFORM LESION S T AG E 2 (i.e., 5 identical monomers) Ca2+-activated chloride channel Vitelli
Slide 12: OPGx-BEST1 Gene Therapy is Designed to Target RPE and Restore Bestrophin Function
OPGx-BEST1 Gene Therapy is Designed to Target RPE and Restore Bestrophin Function • Designed to restore retinal ion homeostasis in bestrophinopathies, ameliorating retinal structural OPGx-BEST1 Gene Therapy and functional deficits • BEST1 is targeted using the AAV2 capsid employed Vector AAV2 in LUX
Slide 13: OPGx-BEST1 Program Highlights
OPGx-BEST1 Program Highlights Promising results in Cohort 1 (1.5x109 vg/eye) with over-enrollment in Cohort 2 (4.5x109 vg/eye) • Well-tolerated with no SAEs, no DLTs, and no intraocular inflammation • Structural and functional improvements at 3 months • Cohort 2 overenrolled at 8 participants, weigh
Slide 14: OPGx-BEST1 Phase 1/2 Trial (BIRD-1) Low Dose Cohort Results
OPGx-BEST1 Phase 1/2 Trial (BIRD-1) Low Dose Cohort 1 Results 14
Slide 15: OPGx-BEST1: Phase 1/2 Study Overview (BIRD-1)
OPGx-BEST1: Phase 1/2 Study Overview (BIRD-1) Adaptive, open-label, dose-exploration, safety and tolerability study of subretinal injection of Design OPGx-BEST1 in adult participants with BVMD or ARB Dosing 1. Cohort 1: 1.5x109 vg/eye Cohorts 2. Cohort 2: 4.5x109 vg/eye • Primary: Safety and tolerab
Slide 16: Participant Demographics: Low-Dose Cohort 1
Participant Demographics: Low-Dose Cohort 1 101-101 101-104 102-101 102-102 101-106 Age 63 59 50 45 31 Sex Female Female Male Male Male BEST phenotype ARB ARB BVMD BVMD BVMD Baseline VA* (study eye † ) 1 50 49 61 47 Baseline VA* (fellow eye) 43 65 68 72 56 Follow-up duration 6 months 6 months 3 mon
Slide 17: Study Endpoints
Study Endpoints • Measures pointwise sensitivity of the retina over the lesion Microperimetry • Recent natural history data shows a steady decline over 5 years in BVMD, with most of the decline in the area on the edge of the lesion1 B C VA & L LVA • Methods to measure central fine visual function •
Slide 18: Safety and Efficacy Summary: Proof-of-Concept Results from Low-Dose Cohort 1
Safety and Efficacy Summary: Highly Encouraging Proof-of-Concept Results from Low-Dose Cohort 1 Safety • OPGx-BEST1 was well-tolerated in 5/5 participants, with no SAEs or DLTs • 80% of participants (4/5) had structural improvements: Structural • BVMD: 67% of participants (2/3) had a decrease in vit
Slide 19: OPGx-BEST1 Demonstrated a Favorable Safety Profile
OPGx-BEST1 Demonstrated a Favorable Safety Profile • Well-tolerated in 100% of participants No intraocular inflammation • No intraocular inflammation was observed in any patient • No serious adverse events at any study visit • No dose-limiting toxicities 101-101 101-104 • No treatment-related system
Slide 20: Participant-Level Improvement by Endpoint
Participant-Level Improvement by Endpoint* Endpoint 101-101 101-104 102-101 102-102 101-106 ARB ARB BVMD BVMD BVMD BCVA ≥5 letter improvement compared to baseline and fellow eye ✓ ✓ ✓ LLVA ≥5 letter improvement compared to baseline and fellow eye ✓ ✓ Contrast Sensitivity ≥0.2 logMAR improvement from
Slide 21: Change from Baseline in BCVA (ETDRS Letters)
Mean BCVA Improved from Baseline Through 3 Months in Cohort 1 8 6 +5 Letters Change from Baseline in BCVA 4 All Treated Eyes (N=5) (ETDRS Letters) 2 All Fellow Eyes (N=5) Treated Eyes with Structural Improvement (N=4)* 0 Corresponding Fellow Eyes (N=4)* -2 -2 Letters -4 -6 Baseline M1 M3 *Excludes P
Slide 22: Microperimetry Showed BVMD Improvement in the Treated RPE Transitional Zone
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 75% 3/4 evaluable participants* demonstrated retinal sensitivity improvement† in the Transitional Zone are structu
Slide 23: Structural Improvements Seen in BVMD and ARB Participants
Structural Improvements Seen in BVMD and ARB Participants • BVMD: 67% of participants (2/3) had reduction in vitelliform Photoreceptors S T AG E 1 material on multimodal imaging Pre-vitelliform Retinal Pigment Epithelium VITELLIFORM DEPOSITS Bruch’s Membrane Choriocapillaris • All three BVMD partici
Slide 24: Participant 101-106 (BVMD): Microperimetry Improvements
Participant 101-106 (BVMD): Microperimetry Improvements • Threshold for success: ≥3 dB Baseline • Average improvement in TTZ = 3.125 dB • Fellow eye TZ = 0.5 dB • 7 loci had ≥3 dB improvement (circled) This participant met the microperimetry threshold for success of ≥3 dB Month 3 Treated transitiona
Slide 25: Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry
Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry Improvements Baseline Vitelliform lesions reduced Month 3 Baseline Month 3 Lesion reduction consistent with improved function of RPE cells and treatment activity as indicated in microperimetry improvements 25
Slide 26: Participant 102-102 (BVMD): Microperimetry Improvements
Participant 102-102 (BVMD): Microperimetry Improvements Baseline Baseline • Threshold for success: ≥3 dB • Average improvement in TTZ = 3.5 dB Month • Fellow eye3 TZ = 0.5 dB • 6 loci had ≥3 dB improvement (circled) – clustered within the TTZ Month 3 This participant met the microperimetry threshold
Slide 27: Participant 102-102 (BVMD): Microperimetry Improved in Treated RPE Transitional Zone
Participant 102-102 (BVMD): Microperimetry Improved in the Treated RPE Transitional Zone Baseline Baseline Month 3 Month 3 Baseline Month 3 Vitelliform material Fixation moves to a more decreased natural location in the fovea Yellow box represents treated transitional zone. 27 BVMD, best vitelliform
Slide 28: Participant 102-101 (BVMD): Photoreceptor and RPE Atrophy
Participant 102-101 (BVMD): Photoreceptor and RPE Atrophy Limit Improvement 3 Months Baseline 1 Month • Most advanced BVMD participant • Sub-RPE atrophy and scarring, exclusionary from a potential pivotal trial • Vitelliform material changes over time • CS improvements* akin to observations in geogr
Slide 29: Participant 101-101 (ARB): Functional and Structural Outcomes Through 6 Months
Participant 101-101 (ARB): Functional and Structural Outcomes Through 6 Months Participant 101-101 (ARB): Functional and Structural Outcomes Through 6 Months BL M1 M2 M3 M4 M5 M6 15 12 (Letters equivalent) BCVA CFB 10 9 9 Study Eye - OS (Treated) Fellow Eye - OD (Untreated) • Functional 5 improvemen
Slide 30: Participant 101-104 (ARB): Microperimetry Improvement
Participant 101-104 (ARB): Microperimetry Improvement Baseline • Threshold for success: ≥3 dB • Average improvement in area of IRF = 3.3 dB • Fellow eye corresponding area = 2.3 dB • 16 loci had ≥3 dB improvement (circled) – clustered within the TTZ Month 6 This participant met the microperimetry th
Slide 31: Participant 101-104 (ARB): IRF Improvement Co-localized with Microperimetry Improvement
Participant 101-104 (ARB): IRF Improvement Co-localized with Microperimetry Improvement Baseline Month 6 Fixation moves to a more Two areas of baseline natural location in the fovea intraretinal fluid Yellow circles denote pockets of intraretinal fluid. 31 Total macular intraretinal fluid volume: Ba
Slide 32: OPGx-LCA5
OPGx-LCA5 Alan, LCA5 patient
Slide 33: LCA5: Early-onset, Severe IRD with Early Vision Loss
LCA5: Early-onset, Severe IRD with Early Vision Loss • Very early onset severe disease typically LCA5 patients exhibit preserved photoreceptors in the central presenting in infancy or early childhood1 retina in adulthood despite disease severity and early onset Overview & • LCA5 represents ~2% of al
Slide 34: OPGx-LCA5 Gene Therapy is Designed to Restore a Key Protein of the Visual Cycle
OPGx-LCA5 Gene Therapy is Designed to Restore a Key Protein of the Visual Cycle • Lebercilin is a ciliary protein critical for the function of photoreceptor inner and outer segments1 OPGx-LCA5 Gene Therapy • In LCA5 patients, photoreceptor function is severely impaired due to a lack of functioning V
Slide 35: OPGx-LCA5 Program Positioned for Rapid Advancement
OPGx-LCA5 Program Positioned for Rapid Advancement Phase 3 Program Status • Enrollment complete with 8 participants able to complete microperimetry testing • 6-month run-in period; participants serve as their own natural history control prior to bilateral treatment • Primary efficacy endpoint is a m
Slide 36: OPGx-LCA5 Phase 1/2 Trial Participant Demographics
OPGx-LCA5 Phase 1/2 Trial Participant Demographics Adult Participants Pediatric Participants Participant # 01-01 01-03 01-04 01-05 01-06 01-07 Age 34 26 19 17 16 17 Gender Female Male Female Female Male Female Study eye Left (OS) Left (OS) Right (OD) Right (OD) Right (OD) Right (OD) treated Baseline
Slide 37: Visual Acuity Maintained in Adults and Improved in Pediatric Cohort
Visual Acuity Maintained in Adults Over 24 Months and Improved Over 6 Months in Pediatric Cohort M e a n C h a n g e f r o m B a s e l i n e i n VA M e a n C h a n g e f r o m B a s e l i n e i n VA Adult Cohort (N=3) Pediatric Cohort (N=3) -0.6 -0.6 Mean CFB in VA [logMAR] -0.5 -0.5 Mean CFB in VA
Slide 38: Full-Field Stimulus Test Demonstrated Durable Vision Improvement
Full-Field Stimulus Test Demonstrated Durable Vision Improvement Mean CFB in Red and Blue FST Mean CFB in Red and Blue FST Adult Cohort (N=3) Pediatric Cohort (N=3) -2 -2 [log phot-cd.s.m-2] -1.6 [log phot-cd.s.m-2] CFB in Red FST -1.6 CFB in Red FST -1.2 -1.2 -0.8 -0.8 -0.4 -0.4 0 0.4 0 0.4 BL M1 M
Slide 39: Treated Eyes Identified More Objects on the Virtual Reality Mobility Test
Treated Eyes Identified More Objects on the Virtual Reality Mobility Test Mean Change from Baseline in MLoMT Mean Change from Baseline in MLoMT Adult Cohort (N=3) Pediatric Cohort (N=3) 12 12 Mean CFB in Number of Objects Identified Mean CFB in Number of Objects Identified 10 10 at All Luminance Lev
Slide 40: Microperimetry Data Provides Evidence of Increased Sensitivity and Movement of Fixation Toward the Fovea
Microperimetry Data Provides Evidence of Increased Sensitivity and Movement of Fixation Toward the Fovea BL BL M12 M6 M24 M12 Adult Participant 01-04 Pediatric Participant 01-06 Microperimetry is a detailed, eye-tracking-assisted visual field test that creates a retinal sensitivity map of the macula
Slide 41: OPGx-RDH12 OPGx-MERTK OPGx-RHO
OPGx-RDH12 OPGx-MERTK OPGx-RHO
Slide 42: RDH12: An Early-Onset Inherited Retinal Degeneration
RDH12: An Early-Onset Inherited Retinal Degeneration • Mutations in RDH12 cause a severe form of LCA, which leads to early, rapid vision loss in infancy/childhood, often resulting in legal blindness before the third decade of life1 • Most frequent phenotype of RDH12 is autosomal recessive/LCA2 Overv
Slide 43: MERTK: Early-onset Inherited Retinal Disease with Rapid Vision Loss
MERTK: Early-onset Inherited Retinal Disease with Rapid Vision Loss • Severe form of autosomal recessive RP, which has an early-onset (childhood or adolescence) and results in rapid vision loss1 Overview & • Accounts for ~2% of all autosomal recessive RP cases1 prevalence • Global prevalence*: ~21,9
Slide 44: RHO: Highly Variable, Often Slowly Progressive Rod-Cone Dystrophy
9/29/2026 RHO: Highly Variable, Often Slowly Progressive Rod-Cone Dystrophy • Autosomal dominant RP is the most common autosomal dominant retinal disease1 • More than 290 identified RHO mutations1 Overview & • Variants in RHO are the most frequent cause of prevalence adRP (~20-30% of cases) 1 • Glob
Slide 45: Leveraging an Efficient Platform for Clinical and Commercial Success
Leveraging an Efficient Platform for Clinical and Commercial Success Highlights Financials • Multi-asset pipeline with potential first • Ticker: IRD mover advantage in target IRDs • Cash balance: $89 million • Five gene therapy programs expected in • Cash runway extends into 2029 and is the clinic b
Slide 46: Nasdaq: IRD
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Slide 47: Appendix
Appendix OPUS
Slide 48: 101-106 Microperimetry
101-106 Microperimetry Baseline Month 3 48
Slide 49: 102-102 Microperimetry
102-102 Microperimetry Baseline Month 3 49
Slide 50: 101-104 Microperimetry
101-104 Microperimetry Baseline Month 6 50