Opus Genetics (NASDAQ: IRD) maps fully funded IRD gene therapy milestones into 2029

Rhea-AI Filing Summary

Opus Genetics, Inc. furnishes an investor presentation from its Virtual R&D Science Forum, outlining its inherited retinal disease (IRD) gene therapy strategy and pipeline. The company highlights seven AAV-based programs targeting LCA5, BEST1, RDH12, MERTK, RHO, NMNAT1 and CNGB1, with worldwide rights to all programs.

Management states Opus is fully funded into 2029 to advance five IRD clinical programs through potential product approvals and Priority Review Voucher opportunities. Key near-term milestones include a PDUFA date in October 2026 for a partnered phentolamine sNDA, BEST1 Cohort 1 three‑month results in September 2026, Phase 3 dosing for LCA5 in Q4 2026, and initial RDH12 and MERTK clinical study initiations between Q4 2026 and Q1 2027. Four clinical data readouts are expected in 2027.

The presentation details disease biology, prevalence and preclinical data for RDH12, MERTK, RHO, LCA5 and BEST1, along with patient‑reported outcomes from the OPGx‑LCA5 study showing maintained or improved visual acuity and functional vision gains in small adult and pediatric cohorts. Opus also emphasizes global IRD prevalence, strategic partnerships for trial recruitment, and a dose‑exploration, data‑driven clinical development approach.

Insights

Biotech equity analyst

Opus presents a fully funded IRD gene therapy pipeline with defined 2026–2027 milestones.

Opus Genetics outlines a portfolio of AAV gene therapies for inherited retinal diseases, with programs spanning LCA5, BEST1, RDH12, MERTK, RHO, NMNAT1 and CNGB1. Management indicates current cash runway into 2029, supporting five clinical programs through potential approvals and Priority Review Voucher opportunities.

The deck specifies a October 2026 PDUFA date for a partnered phentolamine sNDA, BEST1 Cohort 1 three‑month data targeted for September 2026, and clinical starts for LCA5 Phase 3, RDH12 and MERTK between Q4 2026 and Q1 2027, with four data readouts anticipated in 2027. Early OPGx‑LCA5 data in small cohorts show maintained or improved visual acuity, FST gains and patient‑reported functional benefits.

The presentation also quantifies target populations, such as global prevalence of about 30,900 RDH12 patients and 21,960 MERTK patients, and describes recruitment partnerships, particularly in the Middle East for MERTK. Actual impact will depend on successful trial execution, safety and efficacy outcomes, and regulatory decisions over the 2026–2027 timeframe.

8-K Event Classification

2 items: 7.01, 9.01

2 items

Item 7.01 Regulation FD Disclosure Disclosure

Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.

Item 9.01 Financial Statements and Exhibits Exhibits

Financial statements, pro forma financial information, and exhibit attachments filed with this report.

Key Figures

Cash runway: Into 2029 Phentolamine sNDA PDUFA date: October 2026 BEST1 Cohort 1 initial data: September 2026 +5 more

8 metrics

Cash runway Into 2029 Funds five IRD clinical programs through potential approvals and PRVs

Phentolamine sNDA PDUFA date October 2026 Partnered phentolamine ophthalmic solution 0.75% for presbyopia

BEST1 Cohort 1 initial data September 2026 Three‑month results from first BEST1 cohort

Planned LCA5 Phase 3 dosing start Q4 2026 OPGx‑LCA5 Phase 3 dosing initiation

Planned RDH12 clinical start Q4 2026 OPGx‑RDH12 clinical study initiation in U.S.

Global RDH12 prevalence ~30,900 patients Across U.S., EU4+UK, Middle East/North Africa and China

Global MERTK prevalence ~21,960 patients Across U.S., EU4+UK, Middle East/North Africa and China

U.S. BEST1 prevalence 8,400 patients Includes ~8,000 BVMD and ~400 ARB cases in the U.S.

Key Terms

Priority Review Voucher, PDUFA date, Orphan Drug exclusivity, structure-function dissociation, +2 more

6 terms

Priority Review Voucher regulatory

"All gene therapy programs have the potential to qualify for a Priority Review Voucher"

A priority review voucher is a transferable regulatory incentive that lets a company move a future drug or device application to the front of the review line, shortening the review period by several months. For investors it matters because the voucher can speed up market access for a high-value product or be sold to other companies for significant cash, acting like a tradable fast-pass that can accelerate revenue or create immediate financial upside.

PDUFA date regulatory

"Oct 2026 PDUFA date for Phentolamine sNDA"

PDUFA date is the deadline the U.S. Food and Drug Administration sets to complete its review of a drug or biologic application and decide whether to approve it. Investors watch it like a court verdict date: the decision can unlock sales and growth if approved or sharply reduce expected value if denied, so markets often move significantly as the date approaches or when the outcome is announced.

Orphan Drug exclusivity regulatory

"Broad IP protection and eligible for Orphan Drug exclusivity"

A regulatory right that gives a drugmaker sole approval to market a medicine for a specific rare disease for a set number of years, during which the regulator will not approve the same medicine from competitors for that same use. For investors, this is like a temporary exclusive sales permit that can protect revenue and justify higher valuation because it reduces near‑term competition and helps the company recover development costs and capture market share.

structure-function dissociation medical

"Structure-Function Dissociation: The Clinical Imperative"

Full-field stimulus test medical

"Full-Field Stimulus Test Demonstrated Durable Vision Improvement"

multi-luminance orientation and mobility test medical

"MLoMT, multi-luminance orientation and mobility test"

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false000122862700012286272026-06-162026-06-16

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): June 16, 2026

Opus Genetics, Inc.

(Exact name of registrant as specified in its charter)

Delaware	001-34079	11-3516358
(State or other jurisdiction of incorporation)	(Commission File Number)	(IRS Employer Identification No.)

8 Davis Drive Durham, NC		27713
(Address of principal executive offices)		(Zip Code)

(984) 884-6030

(Registrant’s telephone number, including area code)

N/A

(Former name or former address, if changed since last report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.0001 par value per share	IRD	The Nasdaq Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter). Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Item 7.01 Regulation FD Disclosure.

As previously announced, management of Opus Genetics, Inc., a Delaware corporation (the “Company”), delivered a corporate presentation at its Virtual R&D Science Forum held on June 16, 2026. A webcast of the presentation is accessible through the investor relations section of the Company’s website. The presentation is attached hereto as Exhibit 99.1 and incorporated herein by reference. The Company has also made the presentation available to investors on the “Events” section of the Company’s website at https://ir.opusgtx.com.

The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1, is furnished and shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), nor shall such information be deemed incorporated by reference in any filing made by the Company under the Securities Act of 1933, as amended, or the Exchange Act, whether made before or after the date hereof, except as expressly set forth by specific reference in such a filing. The Company undertakes no obligation to update, supplement, or amend the materials attached hereto as Exhibit 99.1.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.	Description
99.1	Virtual R&D Science Forum Corporate Presentation.
104.1	Cover Page Interactive Data File (embedded within Inline XBRL document).

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

	OPUS GENETICS, INC.
Date: June 16, 2026	By:	/s/ Dr. George Magrath
	Name:	Dr. George Magrath
	Title:	Chief Executive Officer

Exhibit 99.1

 Opus Genetics R&D Science Forum  June 16, 2026 | 10:00 AM – 12:00 PM ET 

 Certain statements contained in this presentation are not statements of historical fact and are forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements give current expectations or forecasts of future events or our future financial or operating performance. Such statements include, but are not limited to, statements concerning our data from and future enrollment for our clinical trials, our pipeline of additional indications and anticipated regulatory milestones.   In some cases, you can identify forward-looking statements by the following words: “aim,” “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “ongoing,” “plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of those terms, and similar expressions that convey uncertainty of future events or outcomes to identify these forward-looking statements.  These forward-looking statements reflect our management’s beliefs and views with respect to future events, are based on estimates and assumptions as of the date of this presentation and are subject to risks and uncertainties, many of which are beyond our control, that could cause our actual results to differ materially from those in these forward-looking statements, including, without limitation: our gene therapy product candidates are based on a novel technology and manufactured by a third party, which may result in delays and difficulties in obtaining regulatory approval; our planned clinical trials may face substantial delays, result in failure, or provide inconclusive or adverse results that may not satisfy U.S. Food and Drug Administration (“FDA”) requirements to further develop our therapeutic products; delays or difficulties associated with patient enrollment in clinical trials may affect our ability to conduct and complete those clinical trials and obtain necessary regulatory approvals; changes in regulatory requirements could result in increased costs or delays in development timelines; we depend heavily on the success of our product pipeline; if we fail to find strategic partners or fail to adequately develop or commercialize our pipeline products, our business will be materially harmed; others may discover, develop, or commercialize products similar to those in our pipeline before or more successfully than we do or develop generic variants of our products even while our product patents remain active, thereby reducing our market share and potential revenue from product sales; we do not currently have any sales or marketing infrastructure in place and we have limited drug research and discovery capabilities; the future commercial success of our products could significantly depend upon several uncertain factors, including third-party reimbursement practices and the existence of competitors with similar products; product liability lawsuits against us or our suppliers or manufacturers could cause us to incur substantial liabilities and could limit commercialization of any product candidate that we may develop; failure to comply with health and safety laws and regulations could lead to material fines; we have not generated significant revenue from sales of any products and expect to incur losses for the foreseeable future; our future viability is difficult to assess due to our short operating history and our future need for substantial additional capital, access to which could be limited by any adverse developments that affect the financial markets; raising additional capital may cause our stockholders to be diluted, among other adverse effects; instability and operational disruptions at government agencies, such as the FDA, may adversely impact our development and commercialization plans by causing delays and requiring the use of additional, unforeseen resources to obtain regulatory approval for trials or products in our pipeline; we operate in a highly regulated industry and face many challenges adapting to sudden changes in legislative reform or the regulatory environment, including due to government shutdowns and disruptions at government agencies, which cause delays, requires the use of additional, unforeseen resources, affects our pipeline stability, and could impair our ability to compete in international markets; we may not receive regulatory approval to market our developed product candidates within or outside of the U.S.; with respect to any of our product candidates that receive marketing approval, we may be subject to substantial penalties if we fail to comply with applicable regulatory requirements; our potential relationships with healthcare providers and third-party payors will be subject to certain healthcare laws and regulations, which could expose us to extensive potential liabilities; we rely on third parties for material aspects of our business, such as conducting our nonclinical and clinical trials and supplying and manufacturing bulk drug substances, which exposes us to certain risks; we may be unsuccessful in entering into or maintaining licensing arrangements or establishing strategic alliances on favorable terms, which could harm our business; inadequate patent protection for our product candidates may result in our competitors developing similar or identical products or technology, which would adversely affect our ability to successfully commercialize; we may be unable to obtain full protection for our intellectual property rights under U.S. or foreign laws; we may become involved in lawsuits for a variety of reasons associated with our intellectual property rights, including alleged infringement suits initiated by third parties; we are dependent on our key personnel, and if we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy; as we grow, we may not be able to operate internationally or adequately develop and expand our sales, marketing, distribution, and other corporate functions, which could disrupt our operations; the market price of our common stock is expected to be volatile and if we fail to comply with the continued listing standards of Nasdaq, our common stock may be delisted; and factors out of our control related to our securities, such as securities litigation or actions of activist stockholders, could adversely affect our business and stock price and cause us to incur significant expenses.  We discuss many of these risks in greater detail under Part I, Item 1A “Risk Factors” in our Annual Report on Form 10-K for the year ended December 31, 2025 and in subsequent reports filed with or furnished to the Securities and Exchange Commission. Moreover, we operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. Given these uncertainties, you should not place undue reliance on these forward-looking statements.  Any forward-looking statement in this presentation speaks only as of the date hereof or as of the date specified herein. We undertake no obligation to publicly update any forward-looking statement, whether as a result of new information, future developments or otherwise, except as may be required by applicable laws or regulations.  Disclosures and Forward-Looking Statements  2 

  Meet Our Speakers  George Magrath, MD  Chief Executive Officer  Ben Yerxa, PhD  President  Sally Tucker, PhD  Chief Medical Officer  Ash Jayagopal, PhD, MBA   Chief Scientific & Development Officer  Joe Schachle, MBA Chief Operating Officer  Jean Bennett, MD, PhD  University of Pennsylvania  Kenneth Fan, MD, MBA  Retina Consultants of Texas  Professor Robert MacLaren  University of Oxford  Lejla Vajzovic, MD  Duke University  Todd Durham, PhD, MS  Foundation Fighting Blindness  Opus Genetics Leadership  Key Opinion Leaders  Bart Leroy, MD, PhD  Ghent University Hospital  3 

 Agenda – Part 1  Topic  Speaker(s)  Company Introduction  George Magrath, MD  Jean Bennett, MD, PhD  RDH12  Kenneth Fan, MD, MBA  Ash Jayagopal, PhD  MERTK  Professor Robert MacLaren  Ash Jayagopal, PhD  RHO  Lejla Vajzovic, MD  Ash Jayagopal, PhD  Clinical Development Strategy  Sally Tucker, PhD  Q&A  Ben Yerxa, PhD (Moderator)  4 

 Agenda – Part 2  Topic  Speaker(s)  LCA5  Bart Leroy, MD, PhD  BEST1  Ash Jayagopal, PhD  George Magrath, MD  IRD Patient Journey and Disease Prevalence  Joe Schachle, MBA  Patient Recruitment & Retention Panel  Ben Yerxa, PhD (Moderator)  Jean Bennett, MD, PhDTodd Durham, PhD, MS  Bart Leroy, MD, PhD  Q&A  Ben Yerxa, PhD (Moderator)  Summary Takeaways  George Magrath, MD  5 

 Company Introduction  George Magrath, MD  Chief Executive Officer  Opus Genetics 

 The Opus Opportunity: Fully-Funded to Advance 5 IRD Clinical Programs  Portfolio approach produces multiple data readouts and milestones  Follow-on treatments from the first approved IRD gene therapy  Broad IP protection and eligible for Orphan Drug exclusivity  Cost-effective development: Efficient programs with compelling economics  Flexibility & potentially streamlined paths to approval  Non-dilutive & voucher funding plus partnered strategic financial asset  Validated science & delivery approach  7  Targeted IRD AAV gene therapy assets  Mover advantage in multiple indications  1st  Streamlined timelines & capital efficiency  Rare disease regulatory advantages  Revenue & partnership streams drive value  7  AAV, adeno-associated virus; BEST1, bestrophin 1; CNGB1, cyclic nucleotide-gated channel β1; IP, intellectual property; IRD, inherited retinal disease; LCA5, Leber congenital amaurosis 5; MERTK, MER proto-oncogene tyrosine kinase; NMNAT1, nicotinamide mononucleotide adenylyltransferase; RDH12, retinol dehydrogenase 12; RHO, rhodopsin.  LCA5  BEST1  RDH12  MERTK  RHO  CNGB1  NMNAT1 

 IRD Mutations of Interest  Targeting Seven IRD-Causing Gene Mutations  Inherited Retinal Disorders  Retinitis Pigmentosa  Leber Congenital Amaurosis  Bestro-phinopathies  ADRP  RHO  LCA5  NMNAT1  BEST1  BVMD  ARB  LCA  LCA  Targeted Types of IRDs  Targeted IRD Disease Subtypes  Targeted IRD-Causing Gene Mutations  ARRP  MERTK  CNGB1  LCA  RDH12  ADRP, autosomal dominant retinitis pigmentosa; ARRP, autosomal recessive retinitis pigmentosa; BEST1, bestrophin 1; CNGB1, cyclic nucleotide-gated channel β1; IRD, inherited retinal disease; LCA, Leber congenital amaurosis; MERTK, MER proto-oncogene tyrosine kinase; NMNAT1, nicotinamide mononucleotide adenylyltransferase; RHO, rhodopsin; RDH12, retinol dehydrogenase 12.   8 

 Preclinical  IND-enabling  Phase 1/2  Phase 3  Approval  Building a Differentiated Gene Therapy Pipeline  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 Development; FFB, Foundation Fighting Blindness; LCA5, Leber congenital amaurosis 5; NIH, National Institutes of Health; RD, retinal degeneration; RDH12, retinol dehydrogenase 12; RHO, rhodopsin; RP, retinitis pigmentosa; MERTK, MER proto-oncogene tyrosine kinase; NMNAT1, nicotinamide mononucleotide adenylyltransferase.  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  Undisclosed IRD GTx   All gene therapy programs have the potential to qualify for a Priority Review Voucher   9 

 10  Fully-Funded to Support Multiple Clinical Inflection Points  2H 2027  RHO clinical study initiation  Q1 2027  MERTK clinical study initiation  Q4 2026RDH12 clinical study initiation  Q4 2026LCA5 Phase 3 dosing initiation  Oct 2026PDUFA date for Phentolamine sNDA  Sept 2026  BEST1 Cohort 1 3-month results  Current Cash Runway into 2029 Funds Five Clinical Programs Through to Potential Product Approvals and PRV Opportunities  4 Clinical Data Readouts Expected in 2027  Clinical development timelines are based on current estimates and are subject to change; data readouts are targeted for ~9-12 months after study initiation.  Phentolamine ophthalmic solution 0.75% is a commercial partnered program; it is FDA-approved for the treatment of pharmacologically-induced mydriasis; an sNDA has been submitted for the treatment of presbyopia.  BEST1, bestrophin 1; LCA5, Leber congenital amaurosis 5; MERTK, MER proto-oncogene tyrosine kinase; PDUFA, Prescription Drug User Fee Act; PRV, Priority Review Voucher; RDH12, retinol dehydrogenase 12; RHO, rhodopsin; sNDA, supplemental New Drug Application. 

 Scientific OverviewJean Bennett, MD, PhDF.M. Kirby Emeritus Professor of Ophthalmology Perelman School of Medicine, University of PennsylvaniaPhiladelphia, PA 

 12  Inherited Retinal Degeneration Disease Target Selection*  *Assumes gene has been cloned, characterized and intervention is gene-specific.  Optimal Targets  Developmental conditions  Large genes  Slowly progressive disease  Natural history unknown  Asymmetric disease  Extraordinarily rare   Can target affected cells before they have degenerated  Lack of function disease  Small gene/promoter  AAV transduces target cells efficiently  Disease severe enough to detect improvement  Relevant animal/cell model(s)  Quick readout  Relatively prevalent  More Challenging  Spark Therapeutics  377  348  RPE65  CHM 

 13  Treat the function to reverse pathology and restore or preserve vision  Structure-Function Dissociation: The Clinical Imperative  Targeting Diseases Where the Structure is Intact  Retinal structure is relatively preservedeven 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  Pick the right patients, and choose meaningful endpoints for our clinical trials  Clinical evidence for curative potential in IRDs  AAV, adeno-associated virus; IRD, inherited retinal disease. 

 14  Inspiration from Patients and Families  LCA-RDH12 Kids  LCA-LCA5 and LCA-RDH12:  Ciliopathies  Rare  Imaging: Treatable photoreceptors in childhood, young adults  Animal & cell models  Compared to RPE65:   More severe   Earlier onset  1st to be identified with LCA5  LCA5, Leber congenital amaurosis 5; RPE65, retinal pigment epithelium-specific 65 kDa protein; RDH12, retinol dehydrogenase 12. 

 15  Patient-Academic Partnerships and Opus Genetics: The LCA5 Story  Identification of LCA5  (Nijmegen, 2007)  Proof-of-Concept:  LCA5 Gene Therapy (2018)  Lca5-/- Mouse (P. Nishina)  LCA5 Consortium (2011)  GMP AAV  LCA5 Clinical Trial Initiated (2023)  1990  1995  2000  2005  2025  2020  2015  2010  AAV, adeno-associated virus; GMP, Good Manufacturing Practices; LCA5, Leber congenital amaurosis 5. 

 Abundant Safety Data  >140 retinal gene therapy clinical trials initiated  Gene therapy centers around the world  Thousands of eyes have been injected  Numerous disease targets  Variety of strategies  Excellent safety data  Familiarity with gene therapy surgical procedures, vector handling and storage, genotype-phenotype correlations, outcome measures  Half a dozen retinal gene therapy clinical trials will read out within the next year  Efficacy/Durability Data – LUXTURNA® (voretigene neparvovec-rzyl)  Long-term durability data (>9 years and counting) for Phase 3  Real world efficacy similar to that reported in clinical trials  16  Status of Retinal Gene Therapy  LUXTURNA® is a registered trademark of Spark Therapeutics, Inc. 

 > In the 2000’s  No path/regulatory issues  De-risk safety of subretinal AAV  Accurate dosing (prevent AAV adherence)  Surgical delivery  Lack of genotyped patients  Pediatric subjects  Immune status  FDA requirements:  Injection of contralateral eye  Control group  Lack of natural history data  Lack of relevant outcome measures  Potency assays  Numerous Obstacles to Retinal Gene Therapy Have Been Overcome  > 2026: More Potential Outcome Measures  Multi-Luminance Mobility Test  Navigation  Orientation,   Object Detection  Perimetry  Anatomy  Change in Disease   Progression  Reading the Eye Chart  17  AAV, adeno-associated virus; FDA, Food and Drug Administration; GMP, Good Manufacturing Practices; LCA5, Leber congenital amaurosis 5. 

 RDH12 Overview  Kenneth Fan, MD, MBA Retina Consultants of Texas  Houston, TX 

 Overview & prevalence  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  Accounts for ~3.5-10.5% of all LCA cases1  Global prevalence*: ~30,900 patients3  Middle East / North Africa prevalence: ~17,500 patients3  U.S. prevalence: ~2,500 patients3  Clinical features  Dense intraretinal pigmentation and macular atrophy with yellowish discoloration and pigmentation1,4  Gold foil-like reflectance and watercolor appearance1  Early peripheral RPE atrophy with pigmented deposits, including bone spicules1  Peripapillary sparing1  Symptoms1,4  Loss of peripheral and central vision  Photophobia  Nystagmus  Night blindness  19  RDH12: An Early-Onset Inherited Retinal Degeneration  *Global prevalence estimate includes United States, EU4 (France, Spain, Germany, & Italy), UK, Middle East/North Africa, and China.  LCA, Leber congenital amaurosis; RDH12, retinol dehydrogenase 12; RPE, retinal pigment epithelium.  1. Varela MD, et al. Ophthalmic Genet. 2022;43:301-306. 2. Aleman TS, et al. Invest Ophthalmol Vis Sci. 2018;59:5225-5236. 3. Triangle Insights Analysis 2026. Opus Genetics, Inc. 4. Kumaran N. Br J Ophthalmol. 2017;101:1147-1154.     Images courtesy of Kenneth Fan, MD 

 RDH12 is an enzyme expressed specifically in photoreceptor inner segments1  Plays a key role in clearing toxic byproducts, such as all-trans-retinal, created during the visual process1  When RDH12 is not functioning properly, toxic substances build up and damage retinal cells, leading to progressive vision loss that occurs in LCA1  RDH12 is a Critical Protector of Photoreceptor Health and Function  RDH12 role within photoreceptors. Figure from Varela MD, et al. Ophthalmic Genet. 2022;43:301-306.  20  LCA, Leber congenital amaurosis; RDH12, retinol dehydrogenase 12.  1. Varela MD, et al. Ophthalmic Genet. 2022;43:301-306.  

 Longitudinal studies of RDH12 patients suggest relatively preserved visual acuity with steep decline in second decade of life  Generally, VA maintained to ~20/200 or better for first two decades​  Thereafter, VA steeply declines toward finger counting, light perception only​  Functional signals remain in extramacular rod function and in cone-mediated foveal vision  Extramacular (peripheral) rod function is present even in face of VA decline​  Ideal treatment window is pre-adolescence, but patients up to 2nd decade may benefit prior to steep VA decline  21  RDH12 Structural Changes Define the Therapeutic Window  Structure-function dissociation creates favorable pathobiology for AAV gene replacement in RDH12 similar to RPE65  AAV, adeno-associated virus; ONL, outer nuclear layer; ONL, outer nuclear layer; RDH12, retinol dehydrogenase 12; RPE65, retinal pigment epithelium-specific 65 kDa protein; VA, visual acuity.  Jacobson SG, et al. Invest Ophthalmol Vis Sci. 2007;48:332–338  Generally lower ONL thickness, but improved cone-mediated sensitivity in RDH12 patient (circled region indicates 1.5 log units or 30 times better sensitivity in RDH12 vs RPE65) 

 OPGx-RDH12 Scientific Overview  Ash Jayagopal, PhD, MBA  Chief Scientific and Development Officer   Opus Genetics 

 Success with LUXTURNA® indicates potential restoration of the retinoid cycle can rescue retinal function  Established AAV8 vector, codon optimized transgene, and specific promoter targets photoreceptors  Designed to restore visual cycle function in the inner segments of photoreceptors  OPGx-RDH12 Gene Therapy is Designed to Restore a Key Component of the Visual Cycle   OPGx-RDH12 Gene Therapy  Vector  AAV8  Delivery  Single subretinal injection  23  AAV8, adeno-associated virus serotype 8; RK1, rhodopsin kinase 1.  

 OPGx-RDH12 restored RDH12 protein expression and enzymatic activity in an RDH12 deficient mouse model (RDH12KO) in a dose-dependent manner  Restoration of RDH12 expression and function was achieved in RDH12KO mice (3E10 vg/eye)  OPGx-RDH12 Delivered a Functional RDH12 Enzyme In Vivo   Substrate Conversion (%)  RDH12 in vivo enzyme activity   OPGx-RDH12-mediated expression in RDH12KO mice  RDH12  Tubulin  AAV8, adeno-Associated Virus Serotype 8; HPLC, high-performance liquid chromatography; hRDH12, human retinol dehydrogenase 12; PR, photoreceptor; RDH12, retinol dehydrogenase 12; RDH12KO, retinol dehydrogenase 12 knockout; RGC, retinal ganglion cell; RK1, rhodopsin kinase 1.   Data on file, Opus Genetics, Inc.  24 

 RDH12KO mice lack retinal phenotype observed in human RDH12 IRD  However, mice are susceptible to bright light induced retinal degeneration vs. WT mice1  AAV8 encoding for hRDH12 in RDH12-/- mouse models of light induced retinal degeneration restored structure and function, supporting potential clinical applications1  OPGx-RDH12 Gene Therapy Restored Structure and Function   Preventative treatment of RDH12 with AAV8 restores structure and function (water maze test)2  AAV8, adeno-Associated Virus Serotype 8; hRDH12, human retinol dehydrogenase 12; IRD, inherited retinal disease; RDH12, retinol dehydrogenase 12; WT, wild type.  1. Bian J, et al. Drug Des Devel Ther. 2021;15:3531-3591. 

 MERTK Overview  Professor Robert MacLarenUniversity of Oxford  Oxford, England 

 MERTK: Early-onset Inherited Retinal Disease with Rapid Vision Loss  *Global prevalence estimate includes United States, EU4 (France, Spain, Germany, & Italy), UK, Middle East/North Africa, and China.  MERTK, MER proto-oncogene tyrosine kinase; RP, retinitis pigmentosa.  1. Audo I, et al. Hum Mutat. 2018 Jul;39:887-913. 2. Triangle Insights Analysis 2026. Opus Genetics, Inc.  Images courtesy of Kenneth Fan, MD  27  Overview & prevalence  Severe form of autosomal recessive RP, which has an early-onset (childhood or adolescence) and results in rapid vision loss1  Accounts for ~2% of all autosomal recessive RP cases1  Global prevalence*: ~21,960 patients2  Middle East / North Africa prevalence: ~14,300 patients2  U.S. prevalence: ~2,600 patients2  Clinical features1  Early macular atrophy  Optic disc pallor (often alongside retinal vessel attenuation)  Pigmentary retinopathy  Abnormal autofluorescence of macula or bullseye maculopathy (ring-like macular lesion)  Subretinal deposits  Symptoms1  Peripheral vision loss, followed by central vision  Night blindness  Photophobia  Myopia  Abnormal color vision 

 MERTK is a receptor tyrosine kinase highly expressed on RPE cells  Essential for phagocytosis of photoreceptor outer segments by the RPE  Loss of MERTK function results in impaired phagocytosis, debris accumulation, leading to eventual photoreceptor death and progressive vision loss  28  MERTK is the Metabolic Gatekeeper in the Retina  MERTK, MER proto-oncogene tyrosine kinase; RPE, retinal pigment epithelium.  Shen-Sampas J, et al. Int Ophthalmol Clin. 2021;61:143-148.   Image created by Opus Genetics, Inc. 

 Early and reduced rod photoreceptor function with cones affected later1  Significant, often asymmetric, reduction in VA usually occurs by teenage years, followed by progressive VA loss through adulthood1  MERTK-related IRD is considered a prime candidate for gene therapy because the underlying structure of the retina is preserved in early stages despite functional loss1,2  29  Functional Loss Precedes Structural Degeneration, Creating an Opportunity for Gene Therapy  IRD, inherited retinal disease; MERTK, MER proto-oncogene tyrosine kinase; OCT, optical coherence tomography; RPE, retinal pigment epithelium; VA, visual acuity.  1. Ghazi NG, et al. Hum Genet. 2016;135:327-343. 2. Shen-Sampas J, et al. Int Ophthalmol Clin. 2021;61:143-148.      Autofluorescence shows RPE mottling, pigmentary changes, and vascular attenuation  OCT shows thinning of retina with some preservation of photoreceptors 

 OPGx-MERTK Scientific Overview  Ash Jayagopal, PhD, MBA  Chief Scientific and Development Officer   Opus Genetics 

 Vector  AAV2  Delivery  Single subretinal injection  Same AAV2 capsid used in LUXTURNA®   OPGx-MERTK is designed to restore critical RPE metabolic functions needed for retinal homeostasis  RPE-specificity conferred by promoter technology  31  OPGx-MERTK Gene Therapy is Designed to Restore Critical Retinal Pigment Epithelium Metabolic Functions   AAV2, adeno-associated virus serotype 8; ITR, inverted terminal repeat; RPE, retinal pigment epithelium; VMD2, vitelliform macular dystrophy 2.   OPGx-MERTK Gene Therapy 

 32  Preclinical Studies Provide Evidence of Retinal Preservation of Structure and Function   AAV2, adeno-associated virus serotype 2; hMERTK, human MER proto-oncogene tyrosine kinase; ONL, outer nuclear layer.  LaVail MM, et al. Adv Exp Med Biol. 2016;854:487-93.   Mertkkd mice exhibited rapid loss of photoreceptors and decline in retinal function  AAV2 encoding for hMERTK protected majority of photoreceptor cells from degenerating  Retinal function significantly increased over that in the uninjected control eyes, where the response was almost abolished  Preventative treatment of Merkd mice with AAV2 encoding for hMERTK restored structure (ONL thickness) and function (electroretinography response) 

 33  OPGx-MERTK Preserved ONL Thickness in RCS Rat Model of Retinal Degeneration  RCS naturally-occurring rat model of MERTK models the structural and functional time course of human MERTK degeneration   Exhibits MERTK deficiency in RPE cells, which enables testing of gene therapy interventions  OPGx-MERTK restored retinal structure (photoreceptors) in a dose-dependent manner   Control  Low Dose  Middle Dose  High Dose  Data on file, Opus Genetics, Inc.  ONL, outer nuclear layer; RCS, Royal College of Surgeons.  

 RHO Overview  Lejla Vajzovic, MD  Duke University  Durham, NC 

 Overview & prevalence  Autosomal dominant RP is the most common autosomal dominant retinal disease1  More than 290 identified RHO mutations1  Variants in RHO are the most frequent cause of adRP (~20-30% of cases) 1  Global prevalence*: ~30,200 patients2  U.S. prevalence: ~8,800 patients2  Clinical features1,3  Bone spicule-like pigment  Mottled/granular appearance  Atrophy  Vessel attenuation  Hypoautofluorescent spots along with a hyperautofluorescent macular ring  Symptoms1,3  Early-onset night blindness  Progressive peripheral visual field loss  Decline of central vision in later stages  35  RHO: Highly Variable, Often Slowly Progressive Rod-Cone Dystrophy  6/15/2026  *Global prevalence estimate includes United States, EU4 (France, Spain, Germany, & Italy), UK, Middle East/North Africa, and China.  adRP, autosomal dominant retinitis pigmentosa; RHO, rhodopsin; RP, retinitis pigmentosa;   1. Amaral RAS, et al. Exp. Biol. Med. 251:10893. doi: 10.3389/ebm.2026.10893. 2. Triangle Insights Analysis 2026. Opus Genetics, Inc. 3. Varela MD, et al. Invest Ophthalmol Vis Sci. 2025;66:69.   Images courtesy of Kenneth Fan, MD 

 Misfolded or Dysfunctional Rhodopsin Drives Photoreceptor Stress and Progressive Rod-Cone Degeneration  RHO encodes for rhodopsin, a rod photoreceptor 11-cis-retinaldehyde photopigment located in the outer segment, critical for phototransduction  Mutations in RHO can cause the rhodopsin protein to misfold or function abnormally, leading to progressive photoreceptor degeneration and vision loss seen in adRP  Dominant RHO mutations are typically gain-of-function, necessitating ablate (knockdown) and replace gene therapy strategies, or dominant-negative, which affects wild type rhodopsin protein function  36  adRP, autosomal dominant retinitis pigmentosa; RHO, rhodopsin.  Athanasiou et al. Prog Retin Eye Res. 2018;62:1-23.   36  Schematic illustration of the potential pathogenic consequences caused by rhodopsin mutations 

 Typical pattern of rod degeneration beginning in childhood (accompanied by night blindness) with subsequent degeneration of cones1  Two distinct phenotypes1,2  Class A: Severely abnormal rod function from early life, cystoid changes common  Class B: Maintain rod function into adulthood, structural degeneration progresses from inferior retina (superior field) to central and superior  Photoreceptors are present for a longer time, lending to a meaningful treatment window before complete degeneration1,2  Progressive Peripheral Field Loss Followed By Central Vision Decline  Functional loss2:     Widespread in Class A; localized to superior field in Class B  Rod > cone dysfunction in both classes   Structural loss co-localized with photoreceptor sensitivity losses2  Inferior retina, demonstrating loss inferiorly in Class B2  1. Athanasiou et al. Prog Retin Eye Res. 2018;62:1-23. 2. Aleman et al. Invest Ophthalmol Vis Sci. 2008;49:1580-1590.  37 

 OPGx-RHO Scientific Overview  Ash Jayagopal, PhD, MBA  Chief Scientific and Development Officer   Opus Genetics 

 Vector  AAV5  Delivery  Single subretinal injection  39  OPGx-RHO Gene Therapy is Designed to “Silence and Replace” in Autosomal Dominant RHO  Silence (shRNA820) and replace (RHO820) strategy  Use of AAV5 and rod-specific promoter   Targets expression of codon-optimized human RHO transgene to rod and cone photoreceptors while selectively suppressing the endogenous mutant (and toxic) RHO protein  AAV, adeno-associated virus; RHO, rhodopsin, scAAV5, self-complementary adeno-associated virus serotype 5; WT, wild type.   OPGx-RHO Gene Therapy  

 Canine Model of RHO adRP as a Test Bed for Therapeutic Studies  Canine model of RHO with naturally-occurring heterozygous T4R mutation provides opportunity to test therapeutic interventions  Slow recovery of rod function after light exposure  Mirrors pattern of retinal degeneration in human adRP  Susceptible to light damage and subsequent PR cell death  Acute light exposure can be used to accelerate pathology  40  Retinal topographic changes: Progressive thinning in superior temporal quadrants, reflecting scotomas in adRP patients  Kijas et al.., PNAS 2002  Sudharsan et al.., IOVS 2017  adRP, autosomal dominant retinitis pigmentosa; PR, photoreceptor; RHO, rhodopsin; RPE, retinal pigment epithelium.   40 

 41  OPGx-RHO: Knockdown and Replacement in T4R adRP-RHO Canines  adRP, autosomal dominant retinitis pigmentosa.  Cideciyan AV, et al. Proc Natl Acad Sci USA. 2018;115:E8547-E8556.  

 42  OPGx-RHO Maintained Rod Morphology in TgP23H Retinas  Dose-dependent preservation of rod morphology observed at 20-31 weeks post injection of OPGX-RHO  1.5 x 1010 vg/eye (“mid-low dose”) estimated to be minimal effective dose for rod preservation using immunofluorescence analysis  Data on file. 

 43  OPGx-RHO Maintained Cone Morphology in TgP23H Retinas  Dose-dependent preservation of cone morphology observed at 20-31 weeks post injection of OPGX-RHO  1.5 x 1010 vg/eye (“mid-low dose”) estimated to be minimal effective dose for cone preservation using immunofluorescence analysis  Data on file. 

 Clinical Development Strategy  Sally Tucker, PhD  Chief Medical Officer  Opus Genetics 

 45  Targeting IRDs with Structure-Function Dissociation  Bestrophinopathies  LCA  RP  Age of onset  Childhood (ARB) to adulthood (BVMD)  Birth or infancy  Adolescence to adulthood  Progression  Often slow and variable progression  Severe, early disease and variable progression  Progression over decades  Symptomology  Defective RPE resulting in cone loss  Decreased central vision  Photophobia  Abnormal rod-cone functionality  Decreased central vision  Night blindness  Visual field loss / tunnel vision  Nystagmus  Our goal is to quickly improve or preserve visual function where retinal structure is relatively preserved  ARB, autosomal recessive bestrophinopathy; BVMD, best vitelliform macular dystrophy; IRD, inherited retinal disease; LCA, Leber congenital amaurosis; RP, retinitis pigmentosa; RPE, retinal pigment epithelium. 

 46  Signs and Symptoms Directly Inform Selection of Key Endpoints  Signs  Vessel Narrowing, Pigment Retinopathy, Optic Disc Pallor, RPE Changes  ONL Thinning, Ellipsoid Zone Disruption, IRF/SRF Fluid, Macular Atrophy  Symptoms  Decreased central vision  Night blindness  Visual field loss / tunnel vision  Nystagmus  Photophobia  Key Structural Endpoints  Fundus Photography, Fundus Autofluorescence (FAF)  Spectral Domain Optical Coherence Tomography (SD-OCT)  Key Functional Endpoints  BCVA LLVA FST  Microperimetry  Contrast sensitivity  MLoMT  Static perimetry  Kinetic visual field testing  Pupillometry  QoL parameters  BCVA, best corrected visual acuity; FST, full-field stimulus test, MLoMT, multi-luminance orientation and mobility test; QoL, quality of life. 

 47  Clinical Studies Follow a Dose Exploration, Data-Driven Approach  Cohort 1 – Low Dose  5-6 participants; Adults (and adolescents)  Early efficacy signal allows conversion to a pivotal study  Safety; evaluate efficacy signal at higher dose  Cohort 2/3 –Mid/High Dose  5-6 participants; Adults (and adolescents)  Safety and maximum efficacy signal  Expand cohort to treat additional participants at low dose  Safety and maximum efficacy signal  Representative study design.  Expand cohort to treat additional participants at mid or high dose 

 48  Targeting Initiation of Clinical Testing in All Three Programs within the Next Year  Program  Region  Study Initiation  RDH12  U.S.  Q4 2026  MERTK  Abu Dhabi  Q1 2027  RHO  Global locations  2H 2027  Clinical development timelines are based on current estimates and are subject to change.  MERTK, MER proto-oncogene tyrosine kinase; RDH12, retinol dehydrogenase 12; RHO, rhodopsin. 

 49  Our Strategic Partnerships Provide Path to Accelerated Recruitment  Collaborative platform uniting key patient advocacy groups dedicated to RDH12-related IRDs  RDH12 Fund for Sight in the U.S.   Eyes on the Future in the UK  Partnership with Abu Dhabi Department of Health; MERTK clinical development activities will be conducted at Cleveland Clinic Abu Dhabi   Dedicated genetic testing program; Emerati Genome Program (EGP)   High MERTK patient prevalence in the region (~14,300 in Middle East/Africa vs ~2,600 in the U.S.)  Multiple additional partnerships aim to accelerate and support clinical development and patient enrollment efforts  IRD panel discussion with representative from Abu Dhabi DOH at BIO International  June 24, 2026 in San Diego  DOH, Department of Health; IRD, inherited retinal disease; MERTK, MER proto-oncogene tyrosine kinase; RDH12, retinol dehydrogenase 12. 

 Patient Recruitment and Retention Strategies   Patient education videos  Increase awareness of IRDs and study activities   Clinical trial participation video series  Observational study initiation (prior to treatment) to proactively identify IRD patients   Patient engagement  Involvement in family days and events  Community newsletters  Outreach across patient databases  88% clinical trial dropout rate due to lost to follow‑up, protocol nonadherence, and consent withdrawal2  Globally, more than 80% of clinical trials fail to enroll on time1  IRD, inherited retinal disease.  1. Desai M. Perspect Clin Res. 2020;11:51-53. 2. Poongothai S, et al. Perspect Clin Res. 2023;14:3-9.  Execution of patient advisory boards  Protocol optimization, endpoint selection and optimization, and assessment of burden  Trial participation support programs   Continued trial education  Coaching initiative pilot underway  50 

 51  Patient Commitment to Expanding Awareness of Disease & Treatment 

 Q&A  Moderated by Ben Yerxa  President  Opus Genetics  

 OPGx-LCA5 Update  Bart Leroy, MD, PhD  Ghent University Hospital  Ghent, Belgium 

 LCA5: Early-onset, Severe IRD with Early Vision Loss  Overview & prevalence  Very early onset severe disease typically presenting in infancy or early childhood1  LCA5 represents ~2% of all LCA cases1  Global prevalence*: ~3,240 patients2  U.S. prevalence: ~170 patients2  Clinical features1,3  Pigmentary retinopathy  Macular atrophy  Photoreceptor structure often preserved   Symptoms1,3  Vision loss (typically starting in infancy); often limited to hand motions or light perception  Nystagmus   Hyperopia  Severe and early photoreceptor loss results in severely abnormal or non-detectable visual fields  *Global prevalence estimate includes United States, EU4 (France, Spain, Germany, & Italy), UK, Middle East/North Africa, and China.  LCA, Leber congenital amaurosis; VA, visual acuity. 1. Boldt K, et al. J Clin Invest. 2011;121(6):2169-2180. 2. Triangle Insights Group Analysis, February 2026. 3. Uyhazi KE, et al. Invest Ophthalmol Vis Sci. 2020;61:30.  M/31yrs, 20/300 VA  F/21yrs, light perception  LCA5 patients exhibit preserved photoreceptors in the central retina in adulthood despite disease severity and early onset  54 

 OPGx-LCA5 Gene Therapy is Designed to Restore a Key Protein of the Visual Cycle   OPGx-LCA5 Gene Therapy   Vector  AAV8  Delivery  Single subretinal injection  55  Lebercilin is a ciliary protein critical for the function of photoreceptor inner and outer segments1   In LCA5 patients, photoreceptor function is severely impaired due to a lack of functioning lebercilin1  However, photoreceptors can survive through the third decade of life, suggestive of a broad window for therapeutic intervention2  OPGx-LCA5 is designed to address mutations in the LCA5 gene, which encodes for the lebercilin protein  Clinically derisked AAV8 vector delivers a functional LCA5 gene directly to photoreceptor cells, using same promoter technology as LUXTURNA®  AAV8, adeno-associated virus serotype 8; LCA5, Leber congenital amaurosis 5.   1. Uyhazi KE, et al. Invest Ophthalmol Vis Sci. 2020;61:30. 2. Song JY, et al. Mol Ther. 2018;26:1581-1593. 

 Visual Acuity Maintained in Adults Over 24 Months and Improved Over 6 Months in Pediatric Cohort   Improvement  Improvement  Mean Change from Baseline in VA  Adult Cohort (N=3)  Mean Change from Baseline in VA  Pediatric Cohort (N=3)  BL, baseline; CFB, change from baseline; M, month; VA, visual acuity.  56 

 Full-Field Stimulus Test Demonstrated Durable Vision Improvement   BL, baseline; CFB, change from baseline; FST, Full-field stimulus test; M, month.  Mean CFB in Red and Blue FST Adult Cohort (N=3)  Mean CFB in Red and Blue FST Pediatric Cohort (N=3)  57 

 Microperimetry Data Provides Evidence of Increased Sensitivity and Movement of Fixation Toward the Fovea  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 by testing a patient's response to light at specific points.BL, baseline; M, month.  58  BL  M12  M24  BL  M6  M12 

 Powerful Participant-Reported Outcomes After OPGx-LCA5 Treatment  59  Adult Participants  01-01: Reported being able to identify her children within a larger group of children 1 month after surgery which she previously could not have done.  01-03: Had no formative vision prior to treatment. Reported being able to see his newborn niece for the first time and watch his sister get married.  Described his newfound independence, including his ability to pour a glass of wine and drink it unassisted for the first time in his life.   Has been able to travel independently and, as a result, he acquired a new job, which requires a greater level of independence than he previously had.  01-04*: Reported that since treatment, she no longer requires a cane and can now navigate urban environments independently.  Pediatric Participants  01-05: Reported being able to walk and cook without the assistance of others, and how treatment has helped her in her writing capabilities.  01-06*: Reported a noticeable difference in the visual brightness between his treated and untreated eyes. Able to watch basketball and can see the players and follow the ball instead of watching the score ticker and listening.  01-07: Mostly nonvisual prior to treatment. Reported visiting a local zoo, where she was able to visualize an owl for the first time, and also reported having to learn colors and what a window was in a hotel  Participant-reported outcomes provided in follow up visits in 2025.  *01-04 and 01-06 were able to complete microperimetry. 

 BEST1 Update  Ash Jayagopal, PhD, MBA  Chief Scientific and Development Officer   Opus Genetics 

 61  BEST1: Group of IRDs 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  Global prevalence*: ~21,800 patients2  U.S. prevalence: 8,400 patients (~8,000 BVMD and ~400 ARB)2   Clinical features1,3  Serous retinal detachment  BVMD (most common) is characterized by vitelliform (“egg-yolk”) lesion beneath the macula1  Macular atrophy  CNV  Symptoms3,4  Loss of central vision  Metamorphopsia (distorted vision)  Scotoma (blind spot)  Photophobia4  *Global prevalence estimate includes United States, EU4 (France, Spain, Germany, & Italy), UK, Middle East/North Africa, and China.  ADVIRC, autosomal dominant vitreoretinochoroidopathy; ARB, autosomal recessive bestrophinopathy; BEST 1, bestrophin 1; BVMD, best vitelliform macular dystrophy; CNV, choroidal neovascularization; IRD, inherited retinal disease.  1. Amato A, et al. Saudi J Ophthalmol. 2023;37(4):287-295. 2. Triangle Insights Group Analysis, February 2026. 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.  BVMD  ARB  ADVIRC  Most Common BEST1 Phenotypes 

 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 disrupt cellular ion and fluid homeostasis resulting in electrophysiological abnormalities, RPE dysfunction, and retinal degeneration via:  Fluid accumulation in subretinal space (detachment risk)  Defective clearance of toxic waste products (eg, lipid deposits)  Impaired RPE-photoreceptor interactions (eg, defective phagocytosis)  62  BEST1 Disease Biology  BEST1, bestrophin 1; RPE, retinal pigment epitheliumGuziewicz KE, et al. Prog Retin Eye Res. 2017;58:70-88.   ATROPHY  FRAGMENTED VITELLIFORM MATERIAL  SUBRETINAL FLUID  PSEUDOHYPOPYON  Photoreceptors  Retinal Pigment Epithelium  Bruch’s Membrane  Choriocapillaris  VITELLIFORM LESION  VITELLIFORM DEPOSITS  STAGE 1  Pre-vitelliform  STAGE 2  Vitelliform  STAGE 3  Pseudohypopyon  STAGE 4  Vitelliruptive  STAGE 5  Atrophy/Fibrosis  Stages of BVMD 

 BEST1, bestrophin 1 gene; ARB, autosomal recessive bestrophinopathy; BVMD, Best vitelliform macular dystrophy; ADVIRC, autosomal dominant vitreoretinochoroidopathy.  Haldrup SB, et al. Int J Mol Sci. 2025;26(19).  63  Pathogenic Mechanisms of BEST1 Variants  ↓Reduced protein expression, trafficking, or channel activity  E.g., BEST1 variants in ARB  Mutant protein inhibits normal protein function  E.g., BEST1 variants in BVMD  Mutant protein increases protein activity or introduces new function  E.g., BEST1 variants in ADVIRC (<2% of population, very rare)  Cl-  Cl-  Cl-  Cl-  Cl-  Cl-  Abnormal ion flux  Cl-  Cl-  GAIN-OF-FUNCTION  LOSS-OF-FUNCTION  LOSS-OF-FUNCTION  DOMINANT NEGATIVE  NORMAL  Normal monomer  Mutant monomer  Normal BEST1  RECESSIVE 

 Cl-  Cl-  Cl-  Cl-  Cl-  Cl-  Cl-  Cl-  Abnormal ion flux  Cl-  Cl-  Cl-  Cl-  Cl-  Cl-  Cl-  BEST1, bestrophin 1 gene; ARB, autosomal recessive bestrophinopathy; BVMD, Best vitelliform macular dystrophy; ADVIRC, autosomal dominant vitreoretinochoroidopathy.  Haldrup SB, et al. Int J Mol Sci. 2025;26(19).  64  Most BEST1 Variants May be Amenable to Gene Augmentation   Normal monomer  Mutant monomer  GAIN-OF-FUNCTION  LOSS-OF-FUNCTION  LOSS-OF-FUNCTION  RECESSIVE  DOMINANT NEGATIVE  NORMAL  Introduction of functional BEST1 restores normal function  E.g., ARB  Increasing functional BEST1 expression may overcome mutant protein’s dominant-negative effect  E.g., BVMD  Increasing functional BEST1 does not overcome mutant protein function; may require gene editing  E.g., ADVIRC  Normal BEST1 

 *Treatment-response assessment conducted on applicable mutations.  BEST1, bestrophin 1 gene; pA/pF, picoamperes per picofarad; YFP, yellow fluorescent protein; NaI, sodium iodide.  Sinha D, et al. Am J Hum Genet. 2020;107(2):278-292.   65  Paradigm for Guiding Treatment Decisions   In vitro engineering of cell line with patient-specific BEST1 mutation  Measure BEST1 channel function via two assays  Potential responder  Potential non-responder  Eligible for gene augmentation  Clinical Diagnosis  Genetic Testing to Identify BEST1 Variant  Functional Validation  Treatment-Response Assessment*  Clinician Recommendation  ‘Disease-in-a-dish’ Model  BEST1 channel activity restoration  Gene Augmentation  Persistent BEST1 channel dysfunction  Not eligible for gene augmentation  YFP fluorescence   100  70  40  0  150  300  Time after Nal addition (sec)  Normal BEST1  Patient BEST1  Normal  Patient  C  A 

 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 usually remain viable for decades, providing a wide therapeutic window  OPGx-BEST1 Gene Therapy is Designed to Target RPE and Restore Bestrophin Function  OPGx-BEST1 Gene Therapy  Vector  AAV2  Delivery  Single subretinal injection  66  AAV8, adeno-associated virus serotype 8; RK1, rhodopsin Kinase 1; RPE, retinal pigment epithelium.  

 OPGx-BEST1 Clinical Update  George Magrath, MD  Chief Executive Officer  Opus Genetics 

 *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 Participant Demographics  Participant #  101-101  101-104  102-101  102-102  101-106  Age  63  59  50  45  31  Sex  Female  Female  Male  Male  Male​  BEST phenotype/mutation  ARB  ARB  BVMD  BVMD  BVMD  Study (treated) eye*  Left (OS)  Right (OD)  Left (OS)  Left (OS)  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  68 

 69  Baseline OCT Example: 101-106 (BVMD)  Study Eye(Treated)  Fellow Eye (Untreated)  BVMD, best vitelliform macular dystrophy; OCT, optical coherence tomography. 

 70  Baseline Microperimetry Example: 101-106 (BVMD)  Fellow Eye (Untreated)  Study Eye (Treated)  Sensitivity Map  Fixation Plot  Average Threshold  BVMD, best vitelliform macular dystrophy. 

 IRD Patient Journey & Disease Prevalence  Joe Schachle, MBA  Chief Operating Officer  Opus Genetics 

 72  Patient Perspective: IRD Patient Flow Through Diagnosis & Genetic Testing  IRD, inherited retinal disease.  Sources: Lam, B. L., et al., Genetic Testing and Diagnosis of Inherited Retinal Diseases, Orphanet Journal of Rare Diseases. December 2021; American Academy of Ophthalmology, Guidelines on Clinical Assessment of Patients with Inherited Retinal Degenerations, October 2022; Ahmed, K., et al., Patient Attitudes towards prenatal diagnostic testing for inherited retinal disease, Prenatal Diagnosis, June 2015.  Clinical Evaluation IRD suspected  1  Refer to Retina SpecialistEvaluation supports diagnosis of IRD  2  Engage genetic professionalIRD specialist or ocular genetic counselor  3  Recommend genetic testing  4  Patient agrees to genetic testing  Pathogenic or likely pathogenic variant  Update clinical management as appropriate  Recommend counseling and testing for at-risk members  Determine eligibility for relevant clinical studies  Variants of uncertain significance  Consider testing of family members  Consider retest  No variants, benign variants  No genetic disease or cause identified  Patient chooses not to have genetic testing  Clinical   management  Periodic check in with expert provider 

 Stone, et al1  1,000 IRD families from 40 states in U.S.  Covers large portion of IRDs (104)  Hanany, et al2  Global study of 277K sequence variants across 6 world populations  ONLY recessive for 187 IRDs  Triangle Insights Analysis3   Conducted in 2023  73  Evolution of IRD Prevalence Estimates  Triangle Insights Group Research4  Meta-analysis of published studies completed   Comprehensive literature search yielded >90 unique sources across five geographies of interest  U.S., EU4+UK, China, Japan, ME/NA  Original Primary Sources & Triangle Insights Research   Enhanced Comprehensive Source  EU4 = France, Spain, Germany, & Italy.  IRD, inherited retinal disease; ME, Middle East; NA, North Africa.  1. Stone EM, et al. Ophthalmology. 2017;124:1314-1331. 2. Hanany M, et al. Proc Natl Acad Sci USA. 2020;117:2710-2716. 3. Triangle Insights Analysis, 2023. 4. Triangle Insights Group Analysis, February 2026. 

 IRD Patient Prevalence Across Select Global Markets Provides Significant Opportunity  China  39,600  Middle East/North Africa  45,200  EU4 + UK  12,880  United States  25,770  EU4 = France, Spain, Germany, & Italy. BEST1, bestrophin 1; CNGB1, cyclic nucleotide-gated channel β1; IRD, inherited retinal disease; LCA, Leber congenital amaurosis; MERTK, MER proto-oncogene tyrosine kinase; NMNAT1, nicotinamide mononucleotide adenylyltransferase; RHO, rhodopsin; RDH12, retinol dehydrogenase 12.   Source: Triangle Insights Group Analysis, February 2026.  Gene  U.S.  EU4 + UK  Middle East/North Africa  China  Total Prevalenceby Gene  LCA5  ~170  ~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  74 

 IRD Prevalence May Be Higher Than Current Estimates  BEST1 Prevalence   Analysis based on published studies with diagnostic testing to confirm diagnosis*   Estimated   8,400 Patients   in the U.S.   with BEST1  Patients may not undergo genetic testing when clinicians diagnose BEST1 disease based on the presence of a characteristic vitelliform (“egg-yolk”) lesion beneath the macula  Misdiagnosis may contribute to underestimation of BEST1 prevalence  “Quite a few of my BEST patients have been seen by other physicians in my practice and did not get the diagnosis of BEST disease. I think there are a lot of patients who are not being diagnosed correctly… I would say about 50%.” - Retinal Specialist  BEST1, bestrophin 1; IRD, inherited retinal disease.  Source: Triangle Insights Group Analysis, February 2026.  BEST1 Disease is Likely Underreported  75 

 Patient Recruitment &Retention Panel  Moderator: Ben Yerxa  Panelists: Jean Bennett, MD, PhD  Todd Durham, PhD  Bart Leroy, MD, PhD 

 Q&A 

 Summary Takeaways  George Magrath, MD, MBA, MS  Chief Executive Officer 

 79  Fully-Funded to Support Multiple Clinical Inflection Points  2H 2027  RHO clinical study initiation  Q1 2027  MERTK clinical study initiation  Q4 2026RDH12 clinical study initiation  Q4 2026LCA5 Phase 3 dosing initiation  Oct 2026PDUFA date for Phentolamine sNDA  Sept 2026  BEST1 Cohort 1 3-month results  Current Cash Runway into 2029 Funds Five Clinical Programs Through to Potential Product Approvals and PRV Opportunities  4 Clinical Data Readouts Expected in 2027  Clinical development timelines are based on current estimates and are subject to change; data readouts are targeted for ~9-12 months after study initiation.  Phentolamine ophthalmic solution 0.75% is a commercial partnered program; it is FDA-approved for the treatment of pharmacologically-induced mydriasis; an sNDA has been submitted for the treatment of presbyopia.  BEST1, bestrophin 1; LCA5, Leber congenital amaurosis 5; MERTK, MER proto-oncogene tyrosine kinase; PDUFA, Prescription Drug User Fee Act; PRV, Priority Review Voucher; RDH12, retinol dehydrogenase 12; RHO, rhodopsin; sNDA, supplemental New Drug Application. 

 80  Thank you 

FAQ

What is Opus Genetics (IRD) highlighting in its Virtual R&D Science Forum?

Opus Genetics uses the forum to showcase its AAV gene therapy pipeline for inherited retinal diseases, covering seven gene targets and worldwide program rights. The company also details clinical timelines, patient prevalence data, early LCA5 clinical results, and partnerships supporting global trial recruitment and enrollment.

How long is Opus Genetics (IRD) funded to advance its IRD gene therapy programs?

Opus Genetics states its current cash runway extends into 2029, funding five IRD clinical programs through potential product approvals and Priority Review Voucher opportunities. This funding plan underpins upcoming LCA5, RDH12, MERTK, RHO and BEST1 studies and several planned clinical data readouts through 2027.

What key clinical milestones does Opus Genetics (IRD) expect in 2026 and 2027?

The company targets a PDUFA date for a partnered phentolamine sNDA in October 2026, BEST1 Cohort 1 three‑month results in September 2026, LCA5 Phase 3 dosing and RDH12 trial initiation in Q4 2026, MERTK study initiation in Q1 2027, and four separate clinical data readouts during 2027.

Which inherited retinal diseases and genes are the focus of Opus Genetics’ pipeline?

Opus is developing AAV gene therapies for IRDs driven by LCA5, BEST1, RDH12, MERTK, RHO, NMNAT1 and CNGB1 mutations. These programs address conditions such as Leber congenital amaurosis, bestrophinopathies and retinitis pigmentosa, all characterized by progressive vision loss and often early‑onset disease.

What early clinical results did Opus Genetics report for OPGx-LCA5?

In small adult and pediatric cohorts, OPGx‑LCA5 treatment maintained visual acuity over 24 months in adults and improved it over six months in children. Additional measures, including full‑field stimulus testing and microperimetry, showed increased sensitivity, while patients reported meaningful functional vision gains in daily life.

How large are the target patient populations for Opus Genetics’ IRD programs?

The presentation cites global prevalence estimates such as about 30,900 RDH12 patients, 21,960 MERTK patients, 30,200 RHO patients, 21,800 BEST1 patients and 3,240 LCA5 patients across the United States, EU4 plus UK, Middle East/North Africa and China, illustrating sizeable rare‑disease opportunities.

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