Slide 1: OPGx-BEST1 Gene Therapy Phase 1/2 Study Low Dose Cohort 1 3-month Results
OPGx-BEST1 Gene Therapy Phase 1/2 Study Low Dose Cohort 1 3-month Results September 9, 2026
Slide 2: Disclosures and Forward-Looking Statements
Disclosures and Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,
Slide 3: Management Team and KOL Participant
Management Team and KOL Participant George Magrath, MD Rob Gagnon, CPA, MBA Chief Executive Officer Chief Financial Officer Sally Tucker, MCOptom, PhD Ben Yerxa, PhD Chief Medical Officer President Mark E. Pennesi, MD, PhD, FARVO Ash Jayagopal, PhD, MBA Retina Foundation of the Southwest Chief Scien
Slide 4: OPGx-BEST1 Program and Low-Dose Cohort 1 Clinical Data Highlights
OPGx-BEST1 Program and Low-Dose Cohort 1 Clinical Data Highlights OPGx-BEST1 Cohort 1 & Program Summary T O D AY ’ S T O P I C S • Well-tolerated with no SAEs, no DLTs, and no intraocular inflammation 01 Opus & BEST1 Overview • Structural and functional improvements at 3 months 02 T r i a l D e s i
Slide 5: 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 6: BEST1: Group of Inherited Retinal Diseases with a Range of Onset and Slow Rate of Progression
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 adulthood1 Overview & • Account
Slide 7: 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 8: Trial Design & Topline Cohort Results
Trial Design & Topline Cohort 1 Results Sally Tucker, MCOptom, PhD Chief Medical Officer 8
Slide 9: 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 10: 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 11: 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 12: Safety and Efficacy Summary: Highly Encouraging 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 13: 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 14: 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 15: 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 16: 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 17: 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 18: Post-Treatment Participant Feedback
Post-Treatment Participant Feedback 101-101 Able to see on the eye chart for the first time in 30 years ARB 101-104 Wants the second eye treated ARB 102-101 Happy with the study, mostly stable vision BVMD 102-102 Wants the second eye treated BVMD 101-106 Reports less eye strain after prolonged compu
Slide 19: Participant Case Studies & Next Steps
Participant Case Studies & Next Steps Ash Jayagopal, PhD, MBA Chief Scientific and Development Officer 19
Slide 20: 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 21: Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry Improvements
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 21
Slide 22: 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 23: Participant 102-102 (BVMD): Microperimetry Improved in the 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. 23 BVMD, best vitelliform
Slide 24: Participant 102-101 (BVMD): Photoreceptor and RPE Atrophy Limit Improvement
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 25: 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 26: 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 27: 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. 27 Total macular intraretinal fluid volume: Ba
Slide 28: 4 milestones cleared on the path to pivotal
OPGx-BEST1 Advancing Based on Positive Cohort 1 Results 4 milestones cleared on the path to pivotal 1 2 3 4 Well-tolerated with Efficacy observed on Positive FDA Type C 75% of Cohort 1 no SAEs, no DLTs, both functional and meeting aligned on evaluable participants and no intraocular structural endpo
Slide 29: Program Summary and Next Steps
Program Summary and Next Steps George Magrath, MD Chief Executive Officer 29
Slide 30: Accomplished Significant OPGx-BEST1 Program Milestones
Accomplished Significant OPGx-BEST1 Program Milestones P H 1 / 2 C O H O R T 2 S TAT U S R E G U L AT O R Y S TAT U S Dose A u g u s t 2 0 2 6 F D A Ty p e C m e e t i n g 4.5x109 vg/eye • Aligned on Phase 3 CMC • Constructive dialogue on potential endpoint options Enrollment for Phase 3 Already ove
Slide 31: Current Cash to Support Multiple Clinical Inflection Points
Current Cash to Support Multiple Clinical Inflection Points 2027 Current cash runway extends into BEST1 Pivotal 2029, funding five clinical programs Q2 2027 Study Start through multiple critical inflection points BEST1 Cohort 2 Q1 2027 results MERTK clinical study initiation Q4 2026 RDH12 clinical Q
Slide 32: Nasdaq: IRD
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Slide 33: Mark E. Pennesi, MD, PhD, FARVO
Mark E. Pennesi, MD, PhD, FARVO Leading ophthalmologist, researcher specializing in inherited retinal diseases, and pioneer in gene therapy • Current Appointments • Chief Medical Officer, Steve and Debbie Gray Inherited Retinal Degeneration Endowed Chair; Director, Inherited Retinal Degeneration Cen
Slide 34: Q&A with Opus Management and Dr. Pennesi
Q&A with Opus Management and Dr. Pennesi George Magrath, MD Rob Gagnon, CPA, MBA Chief Executive Officer Chief Financial Officer Sally Tucker, MCOptom, PhD Ben Yerxa, PhD Chief Medical Officer President Mark E. Pennesi, MD, PhD, FARVO Ash Jayagopal, PhD, MBA Retina Foundation of the Southwest Chief
Slide 35: Appendix
Appendix OPUS
Slide 36: BEST1 Market Landscape Quantitative Market Research
BEST1 Market Landscape Quantitative Market Research BEST1 Patients: Estimated Inputs BEST1 Mutation: Estimated Subpopulations Genetic Patient Group Definition Est. Value 46,000 – 87,000 pts BEST1 genotype (with or ~46,000 – 87,000 Genetic without symptoms) patients Symptomatic Diagnosed + 23,600 pts
Slide 37: 101-106 Microperimetry
101-106 Microperimetry Baseline Month 3 37
Slide 38: 102-102 Microperimetry
102-102 Microperimetry Baseline Month 3 38
Slide 39: 101-104 Microperimetry
101-104 Microperimetry Baseline Month 6 39