Opus Genetics : May 2026 Investor Presentation

Published: 2026-05-18 08:39:05 ET IRD

Published on 05/18/2026 at 08:39 am EDT

Delivering on the Promise of Gene Therapy for Rare Inherited Retinal Diseases

May 2026

Nargiza,

BEST1 patient

The Opus Opportunity: A String of Pearls Strategy

Targeted IRD AAV

gene therapy assets

Portfolio approach produces multiple

data readouts and milestones

Validated science & delivery approach

Follow-on treatments from the first approved IRD gene therapy

Mover advantage in

multiple indications

2 of 7 assets in clinical trials: upside

across additional patient populations

Streamlined timelines & capital efficiency

Cost-effective development: efficient programs with compelling economics

Rare disease regulatory advantages

Flexibility & potentially streamlined paths to approval

Revenue & partnership streams drive value

Non-dilutive & voucher funding plus partnered strategic financial asset

LCA5

BEST1

RHO

RDH12

MERTK

CNGB1

NMNAT1

IRD, inherited retinal disease; AAV, adeno-associated virus.

Precision-Targeted, One-Time-Treatment for Rare Diseases

350+ genes known to cause IRDs

World-class science from pioneers in gene therapy

Structure-function biology well-characterized with measurable outcomes amenable to gene augmentation

Rigorous selection of clinical programs

Grounded in natural history studies and patient registries

Validation using large animal models

Single-vector technology for each indication with

clear development paths; not discovery-stage

Faster development path - able to quickly assess efficacy

Proven subretinal delivery with established safety profile and clinical precedent

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 to restore function

Treat the function to reverse pathology and restore or preserve vision

Pick the right patients, and choose meaningful endpoints for our clinical trials

Clinical evidence for curative potential in IRDs

Building a Differentiated Pipeline

OPGx-LCA5 LCA

co-funded by FDA OOPD

OPGx-BEST1

Bestrophinopathies

OPGx-RHO adRP

co-funded by FFB & NIH

OPGx-RDH12 LCA

co-funded by Global RDH12 Alliance

OPGx-MERTK RP

co-funded by FFB RD Fund & Abu Dhabi's

Healthcare Research and Innovation Fund

OPGx-NMNAT1 LCA

OPGx-CNGB1 RP

NIH-funded consortium

Dim light disturbances in keratorefractive patients

te 10/17/26

sNDA PDUFA Da

Presbyopia

FDA Approved Sept 2023

Pharmacologically-induced mydriasis

Opus Genetics owns worldwide rights to all gene therapy programs.

LCA, Leber congenital amaurosis; FDA OOPD, Office of Orphan Products Development; BEST1, bestrophin 1; RHO, rhodopsin; RP, retinitis pigmentosa; FFB, Foundation Fighting Blindness; RDH12, retinol dehydrogenase 12; MERTK, MER proto-oncogene tyrosine kinase; NMNAT1, nicotinamide mononucleotide adenylyltransferase; CNGB1, cyclic nucleotide-gated channel β1.

Actively Advancing Lead Indications

OPGx-BEST1

OPGx-LCA5

Reported 3-month results from sentinel participant

highlighting tolerability and biological activity

Potential treatment for both the dominant and recessive forms of BEST1 disease

Potentially eligible for multiple regulatory designations

Enrollment completed in Phase 1/2 trial with final

participant scheduled for dosing in May 2026

3-month data from Cohort 1 expected in September 2026

Positive Phase 1/2 safety and efficacy results observed in adult and pediatric participants

FDA Progress: Successful Type B RMAT meeting and acceptance into RDEP program

Multiple Regulatory Designations:

Rare Pediatric Disease

Regenerative Medicine Advanced Therapy

Orphan Drug

Potential eligibility for Priority Review Voucher upon BLA approval

Enrollment ongoing in run-in period for planned, adaptive Phase 3 trial

IRD Patient Prevalence Across Select Global Markets Provides Significant Opportunity

United States

25,770

EU4

+ UK

12,880

Middle East/

North Africa

45,200

China

39,600

Gene

U.S. EU4 + UK

Middle East/ North Africa

China

Total Prevalence by Gene

LCA5

~170

~1,400

~1,500

~3,240

BEST1

~8,400

~4,900

~3,600

~4,900

~21,800

RHO

~8,800

~4,600

~2,200

~14,600

~30,200

RDH12

~2,500

~1,000

~17,500

~9,900

~30,900

MERTK

~2,600

~460

~14,300

~4,600

~21,960

NMNAT1

~1,200

~750

~1,100

~2,200

~5,250

CNGB1

~2,100

~1,000

~5,100

~1,900

~10,100

Total Prevalence by Region

~25,770

~12,880

~45,200

~39,600

8 EU4 = France, Spain, Germany, & Italy. Source: Triangle Insights Group Analysis, February 2026.

Juan,

BEST1 patient

BEST1 Mutations are Associated with Retinal Degeneration

Prevalence

~22,000 patients in select global markets incl. 8,400 in the U.S.1

Accounts for ~3.5% of all IRDs2

OPGx-BEST1

Clinical Characteristics

Mutations in BEST1 have been associated with at least five clinically distinct retinal degenerative diseases3

Bestrophinopathy is characterized by retinal lesions, with symptoms including

dimness of vision, metamorphopsia (distorted vision), or scotoma (blind spot)4

Mutations, depending on their impact on BEST1 function, may lead to serous retinal detachment, vitelliform lesions in the macular region, macular atrophy, and loss of central vision

Most bestrophinopathies exhibit a slow rate of decline and central photoreceptors usually remain viable for decades, providing a wide therapeutic window

Designed to restore retinal ion homeostasis in bestrophinopathies, ameliorating retinal structural and functional deficits

Targeted using the AAV2 capsid employed in Luxturna and an RPE-specific promoter

10 1. Triangle Insights Group Analysis, February 2026. 2. Amato A, et al. Saudi J Ophthalmol. 2023;37(4):287-295. 3. Johnson AA, et al. Prog Retin Eye Res.

2017;58:45-69. 4. Tripathy K, et al. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024.

BEST1 Disease Biology: Loss of Bestrophin Channel Function Leads to Retinal Dysfunction and Degeneration

BEST1 gene encodes for Bestrophin-1, a homo-pentameric Ca2+-activated chloride channel critical for RPE maintenance & retinal physiology

Most mutations impart loss-of-function or dominant negative effects that impair protein expression, assembly, or subcellular localization

BEST1 mutants disrupt cellular ion balance culminating in RPE dysfunction & retinal degeneration via:

Defective clearance of toxic waste products (e.g. lipid deposits)

phagocytosis / recycling of outer segments)

HEALTHY STATE

Ca2+ Activated Open Channel

DISEASE STATE

Closed Channel

11 RPE, retinal pigment epithelium; Haldrup SB et al. Int J Mol Sci. 2025;26(19):9421; Pant W et al. PNAS 2025; 122(16) e2424474122

BEST1 IRDs: Clinical Staging and Pathology of Two Main Phenotypes

BVMD

Macular dystrophy similar to AMD

with teen onset

20/60 and worse BCVA observed beginning at Stage 3 disease, leading to choroidal neovascularization, retinal detachment, chorioretinal atrophy

ARB

Fundus

OCT

Pre-vitelliform

Vitelliform

Pseudohypopyon

Vitelliruptive

Atrophy/Fibrosis

Severe, multifocal degeneration beginning in childhood

BVMD, best vitelliform macular dystrophy; ARB, autosomal recessive bestrophinopathy; AMD, age-related macular degeneration; BCVA, best-corrected

visual acuity; IRD, inherited retinal disease; OCT, optical coherence tomography. Agarwal, A and Gass, J.D. Gass' Atlas of Macular Diseases.

Proof of Concept of OPGx-BEST1 AAV2 in a Canine Model of ARB

Robust restoration of RPE-photoceptor interface demonstrated in canine models of ARB using an AAV2.VMD2.hBEST1 construct

Treated cBEST1 models exhibit reversal of lesions and retinal microdetachments, which are hallmarks BEST1 disease

De-risked AAV2 capsid, with AAV2.VMD2 clinical precedent (MERTK) with no known safety issues

Safety/efficacy studies in cBEST1: Regression of lesions and dose-dependent ERG improvement with favorable safety profile supporting clinical dosing

- n=9 dogs at 16-108 weeks, low dose of 1.4E9 vg/eye and high dose of 4.5E9 vg/eye

Lesion onset in area centralis (canine fovea)

AAV2.VMD2.hBEST1

Control injection with BSS

AAV therapy with human transgene

Age: 25 weeks Age: 130 weeks

Age: 19 weeks Age: 114 weeks

Restoration of RPE-PR

interface structure post-treatment vs control

BSS, balanced salt solution; ERG, electroretinogram; MERTK, MER proto-oncogene, tyrosine

kinase; RPE, retinal pigment epithelium. Guziewicz, et al. PNAS. 2018;115:E2839-E2848.

BIRD-1: Phase 1/2 Study of OPGx-BEST1 Subretinal Gene Therapy

Adaptive, open-label, dose-escalation, safety and tolerability study of a subretinal injection of OPGx-BEST1

in adult (≥18 years old) participants with autosomal dominant BVMD or autosomal recessive ARB

Cohort 2: high dose

4.5E9 vg/eye

Efficacy signal at 3 months with no safety concerns as determined by IDMC

+Day 35 IDMC

Safety Eval

Sentinel 4 Further

Participant Participants

(2 BVMD and 2 ARB)

Cohort 1: low dose

1.5E9 vg/eye

+Day 35 IDMC

Safety Eval

Sentinel 4 Further

Participant Participants

(2 BVMD and 2 ARB)

Efficacy signal at 3 months with no safety concerns as determined by IDMC

N o t

A c h i e v e d

Achieved Achieved

Convert to pivotal Phase 3 study

using low dose (1.5E9 vg/eye)

Convert to pivotal Phase 3 study

using high dose (4.5E9 vg/eye)

ARB, autosomal-recessive bestrophinopathy; BVMD, best vitelliform macular dystrophy; DAC, dark-adapted chromatic; EOG, electro-oculogram; IDMC,

Independent Data Monitoring Committee; OCT-A, optical coherence tomography angiography; SD-OCT, spectral domain optical coherence tomography.

Baseline Participant Demographics

Participant #

101-101

101-104

102-101

102-102

101-106

Age

Sex

Female

Male

BEST

phenotype/mutation

ARB

BVMD

Study (treated) eye*

Left (OS)

Right (OD)

Left (OS)

Baseline VA (study/treated eye)

1.68

0.70

0.72

0.49

0.77

Baseline VA (fellow eye)

0.84

0.41

0.34

0.27

0.58

15 *Worse eye deemed study (treated) eye.

ARB, autosomal recessive bestrinopathy; BVMD, best vitelliform macular dystrophy; OD, right eye; OS, left eye; VA, visual acuity.

Baseline OCT Example: 101-106 (BVMD)

Study Eye (Treated)

Fellow Eye (Untreated)

16 OCT, optical coherence tomography.

Baseline Microperimetry Example: 101-106 (BVMD)

Sensitivity Map Fixation Plot Average Threshold

Study Eye

(Treated)

Fellow Eye (Untreated)

OPGx-BEST1 was Well Tolerated in Sentinel Participant (101-101) at 3 Months

Demographics

No ocular inflammation, treatment-related

adverse events, or dose-limiting toxicities

Age

Sex

Female

Diagnosis year

2015

BEST phenotype

ARB

Study (treated) eye

VA at Baseline (OS)

LogMAR 1.66 (CF)

CST at Baseline (OS)

Atrophic macula

Follow-up duration

3 months (to date)

Day 14

Few pigmented cells in vitreous

No AC inflammation

Steroid taper initiated

Postop Month #1

No ocular inflammation

No ocular AEs

No treatment-related AEs or DLT

Postop Month #3

No ocular inflammation

No ocular adverse events

Steroid taper complete

Worse eye deemed study (treated) eye. ARB, autosomal recessive bestrinopathy; BL, baseline; CF, counting fingers; OCT, optical

coherence tomography; OS, left eye; VA, visual acuity. AC, anterior chamber; AE, adverse event; DLT, drug limiting toxicities.

BCVA and CST in the Treated Eye Improved Over 3 Months (101-101)

letter gain

BCVA (Letters)

-2 Baseline Day 14 Month 1 Month 3

-5

CST (μm)

-10

-15

-20

-25

-30

-35

23%

decrease

CST

Baseline Day 14 Month 1 Month 3

Early signal of functional improvement (12 letter gain) observed in the study eye; Participant commented that their vision was no longer "darkening"

Structural improvement (23% decrease)

observed in the study eye

19 BCVA: equivalent letters. BCVA, best-corrected visual acuity; CST, central subfield thickness.

Treated Area Improved Over 3 Months (101-101)

Area of fluid

Baseline

1 Month

Reduction of intraretinal fluid as early as 1 month in areas with less atrophy

3 Month

20 OCT, optical coherence tomography; OS, left eye.

Disclaimer

Opus Genetics Inc. published this content on May 18, 2026, and is solely responsible for the information contained herein. Distributed via Public Technologies (PUBT), unedited and unaltered, on May 18, 2026 at 12:38 UTC.