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: 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,” “estimate,” “expect,” “intend,” “aim,” “m
Slide 3: Management Team and KOL Participants
3 Management Team and KOL Participants Ash Jayagopal, PhD, MBA Chief Scientific & Development Officer Sally Tucker, MCOptom, PhD Chief Medical Officer Rob Gagnon, CPA, MBA Chief Financial Officer Mark E. Pennesi, MD, PhD, FARVO Retina Foundation of the Southwest Dallas, TX George Magrath, MD Chief E
Slide 4: OPGx-BEST1 Program and Low-Dose Cohort 1 Clinical Data Highlights
Well-tolerated with no SAEs, no DLTs, and no intraocular inflammation Structural and functional improvements at 3 months FDA meeting aligned on potential pivotal endpoint >3 dB microperimetry improvement in >5 prespecified loci In conjunction with a RCT using the PGI-S Phase 3 and commercial manufac
Slide 5: Building a Differentiated Gene Therapy Platform
Building a Differentiated Gene Therapy Platform Opus Genetics owns worldwide rights to all gene therapy programs. adRP, autosomal dominant retinitis pigmentosa; BEST1, bestrophin 1; CNGB1, cyclic nucleotide-gated channel β1; FDA OOPD, Food and Drug Administration Office of Orphan Products Developmen
Slide 6: BEST1: Group of Inherited Retinal Diseases with a Range of Onset and Slow Rate of Progression
6 BEST1: Group of Inherited Retinal Diseases with a Range of Onset and Slow Rate of Progression Overview & Prevalence Mutations in BEST1 have been associated with at least five clinically distinct retinal degenerative diseases, with onset from childhood to adulthood1 Accounts for ~3.5% of all IRDs1
Slide 7: 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, a
Slide 8: Trial Design & Topline Cohort Results
8 Trial Design & Topline Cohort 1 Results Sally Tucker, MCOptom, PhD Chief Medical Officer
Slide 9: OPGx-BEST1: Phase 1/2 Study Overview (BIRD-1)
9 ARB, autosomal recessive bestrophinopathy; BVMD, best vitelliform macular dystrophy. OPGx-BEST1: Phase 1/2 Study Overview (BIRD-1) D e s i g n Adaptive, open-label, dose-exploration, safety and tolerability study of subretinal injection of OPGx-BEST1 in adult participants with BVMD or ARB D o s i
Slide 10: Participant Demographics: Low-Dose Cohort 1
*Worse eye deemed study eye. †ETDRS letters equivalent calculated from logMAR ARB, autosomal recessive bestrophinopathy; BEST, bestrophin; BVMD, best vitelliform macular dystrophy; ETDRS, Early Treatment Diabetic Retinopathy Study; OCT, optical coherence tomography; OD, right eye; OS, left eye; VA,
Slide 11: Study Endpoints
11 Study Endpoints Microperimetry Measures pointwise sensitivity of the retina over the lesion 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 lesion* BCVA & LLVA Methods to measure central fine visual function Contrast
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 S a f e t y OPGx-BEST1 was well-tolerated in 5/5 participants, with no SAEs or DLTs S t r u c t u r a l E n d p o i n t s 80% of participants (4/5) had structural improvements: BVMD: 67% of participants (
Slide 13: OPGx-BEST1 Demonstrated a Favorable Safety Profile
Well-tolerated in 100% of participants No intraocular inflammation No serious adverse events No dose-limiting toxicities No treatment-related systemic AEs All ocular treatment-related AEs were mild/moderate in severity No vital sign issues or safety lab findings of note 13 OPGx-BEST1 Demonstrated a
Slide 14: Participant-Level Improvement by Endpoint
Participant-Level Improvement by Endpoint* Endpoint 101-101 ARB 101-104 ARB 102-101 BVMD 102-102 BVMD 101-106 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: Mean BCVA Improved from Baseline Through 3 Months in Cohort 1
2 0 -2 -4 -6 14 12 10 8 6 4 Baseline M1 M3 Change from Baseline in BCVA (Letters Equivalent) All Treated Eyes (N=5) All Fellow Eyes (N=5) Treated Eyes with Structural Improvement (N=4)* Corresponding Fellow Eyes (N=4)* Mean BCVA Improved from Baseline Through 3 Months in Cohort 1 *Excludes Participa
Slide 16: 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 17: Structural Improvements Seen in BVMD and ARB Participants
BVMD: 67% of participants (2/3) had reduction in vitelliform material on multimodal imaging All three BVMD participants had improvements in visual function, with highest gains in areas of vitelliform material reduction ARB: 100% of participants (2/2) had reduction in intraretinal fluid on OCT Both A
Slide 18: Post-Treatment Participant Feedback
Post-Treatment Participant Feedback 101-101 ARB Able to see on the eye chart for the first time in 30 years Wants the second eye treated 102-102 BVMD Wants the second eye treated Reports less eye strain after prolonged computer work; colors on TV appear brighter and clearer Happy with the study, mos
Slide 19: Participant Case Studies & Next Steps
Participant Case Studies & Next Steps Ash Jayagopal, PhD Chief Scientific and Development Officer 19
Slide 20: Participant 101-106 (BVMD): Microperimetry Improvements
Baseline Month 3 Participant 101-106 (BVMD): Microperimetry Improvements 20 BVMD, best vitelliform macular dystrophy; dB, decibel; RPE, retinal pigment epithelium, TTZ; Treated transitional zone. Treated transitional zone follows the vitelliform arc as seen on fundus autofluorescence and OCT Micrope
Slide 21: Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry
Baseline Month 3 Participant 101-106 (BVMD): Vitelliform Material Reduction Co-localized with Microperimetry Improvements 21 BVMD, best vitelliform macular dystrophy; dB, decibel; RPE, retinal pigment epithelium. L e s i o n r e d u c t i o n c o n s i s t e n t w i t h i m p r o v e d f u n c t i o
Slide 22: Participant 102-102 (BVMD): Microperimetry Improvements
Baseline Month 3 Participant 102-102 (BVMD): Microperimetry Improvements 22 BVMD, best vitelliform macular dystrophy; dB, decibel; RPE, retinal pigment epithelium, TTZ: Treated transitional zone. Yellow box represents the treated transitional zone Microperimetry loci were not prespecified Threshold
Slide 23: Participant 102-102 (BVMD): Microperimetry Improved in Treated RPE Transitional Zone
Baseline Month 3 Participant 102-102 (BVMD): Microperimetry Improved in the Treated RPE Transitional Zone Baseline Month 3 B a s e l i n e M o n t h 3 23 Vitelliform material decreased BVMD, best vitelliform macular dystrophy; dB, decibel; RPE, retinal pigment epithelium. Yellow box represents treat
Slide 24: Participant 102-101 (BVMD): Photoreceptor and RPE Atrophy Limit Improvement
Participant 102-101 (BVMD): Photoreceptor and RPE Atrophy Limit Improvement 24 Images are consecutive registered OCT rasters at baseline, 1 month, and 3 months. BVMD, best vitelliform macular dystrophy; OCT, optical coherence tomography; RPE, retinal pigment epithelium; CS, Contrast Sensitivity. CS
Slide 25: Participant 101-101 (ARB): Functional and Structural Outcomes Through 6 Months
P a r a f o v e a l A r e a I n f e r i o r A r e a Baseline Month 3 Month 6 Participant 101-101 (ARB): Functional and Structural Outcomes Through 6 Months Functional improvement maintained to 6 months on BCVA, CS, and LLVA Unable to perform MP due to poor baseline vision IRF decreased at 3 months i
Slide 26: Participant 101-104 (ARB): Microperimetry Improvement
Participant 101-104 (ARB): Microperimetry Improvement Baseline Month 6 26 Total macular IRF volume = 19.06 ul at baseline, 7.55 ul at 6 months. Microperimetry loci were not prespecified ARB, autosomal recessive bestrophinopathy; dB, decibel; IRF, intraretinal fluid; RPE, retinal pigment epithelium.
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 27 Total macular intraretinal fluid volume: Baseline = 19.06 µl, Month 6 = 7.55 µl ARB, autosomal recessive bestrophinopathy; dB, decibel; IRF, intraretinal fluid; RPE, retinal pigment epithelium
Slide 28: Milestones Cleared on the Path to Pivotal OPGx-BEST1
4 milestones cleared on the path to pivotal OPGx-BEST1 Advancing Based on Positive Cohort 1 Results 1 2 3 4 Well-tolerated with no SAEs, no DLTs, and no intraocular inflammation Efficacy observed on both functional and structural endpoints Positive FDA Type C meeting aligned on potential pivotal end
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 D o s e 4.5x109 vg/eye E n r o l l m e n t Already over-enrolled Originally planned for 5 participants Over-enrollment of 8 participants C l i n i c a l D e v e l o p m e n t T i m e l i n e * Dosing expected to
Slide 31: Current Cash to Support Multiple Clinical Inflection Points
Current Cash to Support Multiple Clinical Inflection Points 2027 BEST1 Pivotal Study Start Q1 2027 MERTK clinical study initiation Q4 2026 RDH12 clinical study initiation Q4 2026 LCA5 Phase 3 dosing initiation Oct 2026 PDUFA date for Phentolamine sNDA Sept 2026 BEST1 Phase 1/2 Cohort 1 3-month resul
Slide 32: Opus Genetics
OPUS GE N Eile sy Nasdaq: IRD
Slide 33: Mark E. Pennesi, MD, PhD, FARVO
33 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 Cent
Slide 34: Q&A with Opus Management and Dr. Pennesi
34 Q&A with Opus Management and Dr. Pennesi Ash Jayagopal, PhD, MBA Chief Scientific & Development Officer Sally Tucker, MCOptom, PhD Chief Medical Officer Rob Gagnon, CPA, MBA Chief Financial Officer Mark E. Pennesi, MD, PhD, FARVO Retina Foundation of the Southwest Dallas, TX George Magrath, MD Ch
Slide 35: Appendix
Appendix OPUS
Slide 36: BEST1 Market Landscape: Estimated Patient Populations
36 Triangle Insights Group Research, Q3 2026. BEST1 Market Landscape Quantitative Market Research Patient Group Definition Est. Value Genetic BEST1 genotype (with or without symptoms) ~46,000 – 87,000 patients Symptomatic Diagnosed + undiagnosed (with ocular symptoms) ~23,600 patients Diagnosed (Pos