UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
For the Fiscal Year Ended December 31, 2025
or
For the transition period from _____ to _____
Commission File No. 001-34079
Opus Genetics, Inc.
(Exact name of registrant as specified in its charter)
Registrant’s telephone number, including area code: (984)
884-6030
N/A
(Former name or former address, if changed since
last report)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class Trading Symbol Name of each exchange on which registered
Common Stock, $0.0001 par value per share IRD The Nasdaq Stock Market LLC
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐No☒
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. Yes ☐No☒
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act
of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days: Yes☒ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule
405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ☒ Smaller reporting company ☒
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. ☐
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its
internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. Yes ☐
If
securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the correction of an error to previously issued financial statements. ☐
Indicate
by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of the registrant’s executive officers during the relevant recovery period pursuant to §
240.10D-1(b). ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒
The aggregate market value of the common equity held by non-affiliates of the registrant on June 30, 2025, the last business day of the
registrant’s most recently completed second fiscal quarter, based on the closing price on that date of $0.9421, was approximately $45.9
million. As of March 5, 2026, there were 71,149,045 shares of the registrant’s common stock outstanding.
Documents Incorporated by Reference
Portions of the registrant’s Definitive Proxy Statement to be filed with the Commission pursuant to Regulation 14A in connection with the registrant’s 2026 Annual
Meeting of Stockholders are incorporated by reference into Part III of this report. Such Definitive Proxy Statement will be filed with the Securities and Exchange Commission not later than 120 days after the conclusion of the registrant’s fiscal
year ended December 31, 2025.
Opus Genetics, Inc.
Form 10-K
TABLE OF CONTENTS
PART I 5
ITEM 1. BUSINESS 5
ITEM 1A. RISK FACTORS 46
ITEM 1B. UNRESOLVED STAFF COMMENTS 88
ITEM 1C. CYBERSECURITY 88
ITEM 2. PROPERTIES 89
ITEM 3. LEGAL PROCEEDINGS 89
ITEM 4. MINE SAFETY DISCLOSURES 89
PART II
ITEM 6. [RESERVED] 90
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 108
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 108
ITEM 9A. CONTROLS AND PROCEDURES 108
ITEM 9B. OTHER INFORMATION 109
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 109
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 109
ITEM 11. EXECUTIVE COMPENSATION 109
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 110
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 110
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In this Annual Report on Form 10-K, unless otherwise specified, references to “we,” “us,” “our,” “Opus” or “the Company” mean Opus Genetics, Inc. Our financial statements
are prepared in accordance with accounting principles generally accepted in the United States (“U.S. GAAP”).
FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking statements within the meaning of the safe harbor provisions of Section 27A of the Securities Act of 1933, as
amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as amended (the “Exchange Act”). These forward-looking statements relate to us, our business prospects and our results of operations and are subject to
certain risks and uncertainties posed by many factors and events that could cause our actual business, prospects and results of operations to differ materially from those anticipated by such forward-looking statements. Factors that could cause
or contribute to such differences include, but are not limited to, those described under the heading “Risk Factors” included in this Annual Report on Form 10-K. Readers are cautioned not to place undue reliance on these forward-looking
statements, which speak only as of the date of this report. In some cases, you can identify forward-looking statements by the following words: “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “ongoing,”
“plan,” “potential,” “predict,” “project,” “should,” “will,” “would” or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. We undertake no obligation to revise any
forward-looking statements in order to reflect events or circumstances that might subsequently arise. Readers are urged to carefully review and consider the various disclosures made by us in this report and in our other reports filed with the
U.S. Securities and Exchange Commission (the “SEC”) that advise interested parties of the risks and factors that may affect our business.
SUMMARY RISK FACTORS
Our business is subject to a number of risks, as more fully described in “Item 1A. Risk Factors” in this Annual Report. We are providing the following summary of our principal risk factors to enhance the
readability and accessibility of our risk factor disclosures. We encourage you to carefully review the full risk factors discussed below the summary in their entirety for additional information.
Risks Related to the Development of Our Gene Therapy Products and Other Product Candidates
Risks Related to the Commercialization of RYZUMVI® and Other Product Candidates
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Risks Related to Our Financial Position and Need for Additional Capital
Risks Related to Government Regulation
Risks Related to Our Reliance on Third Parties
Risks Related to Our Intellectual Property
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Risks Related to Our Employee Matters and Managing Growth
Risks Related to Ownership of Our Common Stock
INDUSTRY AND MARKET DATA
In this Annual Report, we reference information, statistics and estimates regarding the medical devices and healthcare industries. We have obtained this information from
various third-party sources, including industry and general publications, reports by market research firms and other sources. This information involves a number of assumptions and limitations, and we have not independently verified the accuracy
or completeness of this information. Some data and other information are also based on the good faith estimates of management, which are derived from our research, review of internal surveys, general information discussed in the industry, and
third-party sources. We believe that these external sources and estimates are reliable but have not independently verified them. The industries in which we operate are subject to a high degree of uncertainty, change, and risk due to a variety
of factors, including those described in “Item 1A. Risk Factors.” These and other factors could cause results to differ materially from those expressed in this Annual Report and other publications.
PART I
ITEM 1. BUSINESS
Opus Genetics, Inc. (the “Company,” “Opus,” “we,” “us,” or “our”) is a clinical-stage biopharmaceutical company developing gene therapies to restore vision and prevent
blindness in patients with inherited retinal diseases (“IRDs”), and other types of therapies for additional ophthalmic disorders.
Opus was founded in February 2018 as Ocuphire Pharma, Inc. and has since undergone the following transactions:
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Pipeline
Our pipeline is composed of a portfolio of gene therapies being developed as durable,
one-time treatments designed to address the underlying genetic causes of severe retinal disorders. The pipeline includes seven adeno-associated virus (“AAV”)-based programs, led by OPGx-LCA5 for LCA5-related mutations and OPGx-BEST1 for
BEST1-related retinal degeneration, with additional candidates targeting RHO, CNGB1, RDH12, NMNAT1, and MERTK. We are also advancing Phentolamine Ophthalmic Solution 0.75%, a small-molecule therapy that is FDA-approved for pharmacologically
induced mydriasis, with additional potential indications in presbyopia and low-light visual disturbances following keratorefractive surgery.
Gene Therapy Approach
Retinal degeneration is a devastating cause of severe vision loss beginning in childhood and progressing into adulthood. It is estimated that over 350,000 people in the
U.S., and approximately 4 to 6 million people worldwide are waiting for treatments for their individual genetic conditions, and more than 350 genes are known to cause inherited retinal diseases. Our IRD programs address mutations in genes that
cause different forms of bestrophinopathy, Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP), and are based on world-class science from gene therapy pioneers at the University of Pennsylvania (including the lab of Dr. Jean
Bennett), Harvard Medical School, and the University of Florida.
By having multiple assets, we are taking a portfolio approach where we believe we will have advantages in our targeted indications. We conduct a rigorous process for
selection of our clinical programs that is grounded in natural history studies and patient registries, and where there is validation using large animal models. For our chosen indications, we aim to ensure structure-function biology that is
well-characterized with measurable outcomes amenable to gene augmentation. Our treatments are designed to target diseases where the structure is intact to treat the function and reverse the pathology in order to restore or preserve vision.
Because we are targeting rare diseases, we believe regulatory advantages may be available from agencies in the U.S. and other countries. This potential flexibility may
allow for streamlined clinical development and paths to approval allowing us to develop the assets in an efficient and cost-effective manner.
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Our treatments are administered via subretinal injection, a proven and reliable delivery method that allows us to directly target the location of disease in the retina.
Gene Therapy Programs
Our gene therapy programs address mutations in genes that cause different forms of Leber congenital amaurosis, bestrophinopathy, and retinitis pigmentosa.
OPGx-LCA5
If approved, our most advanced gene therapy program, OPGx-LCA5 could become the first gene therapy and one-time treatment for
LCA5. The program has received a multi-million-dollar grant from the FDA Office of Orphan Drug Products. The program has also been granted Rare Pediatric Disease, Regenerative Medicine Advanced Therapy (RMAT), and Orphan Drug designations
from the FDA. OPGx-LCA5 is potentially eligible for a Priority Review Voucher from the FDA upon approval of a Biologics License Application (BLA).
LCA5 Disease Characteristics
LCA5 is a severe, early-onset form of IRD that accounts for roughly 2% of all LCA cases, or approximately 170 people in the U.S. and 3,260 people worldwide. There are
currently no approved therapies for LCA5-related inherited retinal degeneration, making gene therapy a potentially transformative approach.
The LCA5 gene encodes for the protein lebercilin, a ciliary protein which is critical for bidirectional protein trafficking in photoreceptor inner and outer segments.
Photoreceptors are retinal cells that enable vision by absorbing light and transducing it into an electrochemical signal that is communicated to the visual centers of the brain. Loss of lebercilin disrupts outer segment development, leading to
profound vision loss early in life.
In LCA5, the outer segments do not properly develop, and photoreceptor function is severely impaired. However, studies in patients with this mutation have reported evidence
for the dissociation of retinal architecture and visual function in this disease, suggesting an opportunity for therapeutic intervention through gene augmentation.
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OPGx-LCA5 Mechanism of Action
OPGx-LCA5 is designed to address a form of LCA due to biallelic mutations in the LCA5 gene. OPGx-LCA5 uses an adeno-associated virus 8 (AAV8) vector to precisely deliver a
functional LCA5 gene to photoreceptors in the outer retina to restore structure and function. OPGx-LCA5 is the same promoter technology as used with LUXTURNA®.
Clinical Development Process and Plan
A Phase 1/2 clinical trial at the University of Pennsylvania is evaluating the safety and preliminary efficacy of OPGx-LCA5 in patients with IRD due to biallelic mutations
in LCA5. Three adults and three pediatric participants were treated. In addition to safety, outcome measures evaluated include measurement of functional vision using: 1) Visual Acuity; 2) Multi-Luminance orientation and Mobility Test (MLoMT), a
virtual reality mobility course; 3) Full-Field Stimulus Test (FST), which measures the retina’s sensitivity to light; and 4) microperimetry, which measures point-wise sensitivity to light.
In September 2023, we dosed the first adult participant in the trial. Upon review of the data from the first three adult patients, the data safety monitoring board
indicated that there was no observed toxicity, and they recommended an adaptive trial design with data-driven dose escalation. Treatment of three pediatric subjects (13-17 years of age) was initiated in February 2025.
In September 2025, we reported the positive results from the six late-stage participants treated with OPGx-LCA5. The data included 3 adult participants treated out to 18
months and 3 pediatric participants treated out to 3 months. OPGx-LCA5 has been well tolerated by all the participants treated, with no ocular serious adverse events and no dose-limiting toxicities observed in any of the treated participants to
date. All ocular adverse events were mild and were anticipated, and there were no events related to the study drug. One pediatric participant presented with a cataract at screening that worsened at three months, which was deemed related to the
surgical procedure and not to the study drug.
In the study, all six participants experienced improvements in vision, providing evidence of biological activity with the
potential for functional restoration of vision in individuals with advanced disease. The three pediatric participants treated over three months demonstrated large gains in cone-mediated vision with improvements across multiple measures of
visual function. In the three adult participants, responses have been observed out to 18 months, underscoring the potential durability of the treatment response. We are planning to present the Phase 1/2 six-month pediatric cohort data at the
annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) conference in May 2026.
On November 6, 2025, we announced the successful completion of a Type B RMAT meeting with the FDA regarding OPGx-LCA5. The meeting provided constructive feedback from the
FDA on key elements of our registration strategy, including Chemistry, Manufacturing and Controls (CMC), and the pivotal trial design. The FDA acknowledged the significant unmet medical need for individuals with LCA5-related blindness and
reaffirmed its commitment to regulatory flexibility for rare genetic diseases.
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The Company will incorporate the FDA’s feedback into its updated clinical development and CMC plans to extend the current trial into a Phase 1/2/3 study to include
enrolling as few as 8 participants in a single arm, 12-month study utilizing an adaptive design, which provides flexibility on endpoints and number of participants, reflective of LCA5 as a rare condition with an urgent medical need.
We expect the Phase 3 portion of the trial will include a run-in period prior to dosing to evaluate the natural history of
each participant to serve as their own control in the study. Recruitment is ongoing with multiple participants enrolled to date for ongoing disease monitoring. Following availability of validated clinical drug supply manufactured with the
intended commercial processes, dosing with OPGx-LCA5 is anticipated in the second half of 2026 with topline clinical data expected approximately one year later.
In September 2025, the FDA introduced the Rare Disease Evidence Principles (RDEP) review process to provide greater speed
and predictability in the review of therapies intended to treat rare diseases with very small patient populations with significant unmet medical need and that are driven by a known genetic defect that is the major driver of the
pathophysiology. With a patient population of fewer than 1,000 individuals, we believe that our LCA5 program meets the eligibility criteria for the RDEP process and we are targeting a submission of an application in the first quarter of
2026.
OPGx-BEST1
OPGx-BEST1 is in development for the treatment of BEST1-associated retinal disease, an IRD that can lead to progressive vision loss and legal blindness. Most
bestrophinopathies exhibit a slow rate of decline and central photoreceptors usually remain viable for decades, providing a wide therapeutic window.
BEST1 Disease Characteristics
Best disease, or vitelliform macular dystrophy, is a rare inherited retinal condition caused by mutations in the BEST1 gene, leading to impaired retinal pigment epithelium
(RPE) function, progressive vision loss, and, in some cases, blindness. BEST1 accounts for ~3.5% of all IRDs and affects an estimated 8,400 people in the U.S. and 22,050 people worldwide. The BEST1 gene encodes for production the bestrophin-1
protein, a channel which governs retinal ion and fluid homeostasis. BEST1 IRDs are characterized by retinal lesions, with symptoms including dimness of vision, metamorphosphia (distorted vision), and areas of vision loss or scotoma (blind
spot).
BEST1 has two main phenotypes: Best Vitelliform Macular Dystrophy (BVMD) and Autosomal Recessive Bestrophinopathy (ARB). ARB is a severe, multifocal degeneration beginning
in childhood while BVMD is a type of macular dystrophy. Vision-threatening complications of BVMD and ARB include choroidal neovascularization, retinal detachment, atrophy, and fibrosis, which may lead to irreversible vision loss and progression
to legal blindness.
OPGx-BEST1 Mechanism of Action and Preclinical Development
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OPGx-BEST1 is designed to target BEST1 using the AAV2 capsid to deliver a functional copy of the BEST1 gene to the retina so that bestrophin-1 protein is produced in RPE
cells. This gene therapy approach aims to restore normal function of the RPE cells such that they can provide proper support to photoreceptors, the cells that detect light. We believe that OPGx-BEST1 could provide long-lasting benefit,
potentially for the lifetime of the patient.
In preclinical studies conducted in a naturally occurring canine model of Best Disease, OPGx-BEST1 provided evidence in support of a first-in-man clinical trial. The
safety/efficacy studies in cBEST1 showed regression of lesions and dose-dependent ERG improvement with favorable safety profile supporting clinical dosing.
Clinical Development Process and Plan
In November 2025, we dosed our first participant in our OPGx-BEST1 Phase 1/2 clinical trial, known as BIRD-1, in patients with BVMD or ARB. The trial is an adaptive,
open-label, dose-exploring, safety and tolerability study. Treatment will be administered via a single subretinal injection in one eye of each participant with two dosing cohorts. The trial will also explore biological activity through
functional and anatomical endpoints, including changes in visual function and retinal structure.
In December 2025, we announced that the Independent Data Monitoring Committee (IDMC) overseeing the trial completed its
pre-specified safety review of the one-month data from the sentinel participant and recommended advancing enrollment and dosing of additional participants in the trial, without modification. Recruitment in the Phase 1/2 study is ongoing at
two clinical sites in the U.S., with three additional sites expected to open. To date, two participants have been treated in the study, representing both dominant and recessive forms of BEST disease, with three-month results from the entire
Cohort 1 expected mid-year 2026.
In February 2026, encouraging data was presented at the Macula Society Annual Meeting detailing results from the first
(sentinel) participant treated with OPGX-BEST1 in the Phase 1/2 study.
This first participant has ARB disease with severe functional impairment. The data demonstrated that OPGx-BEST1 was well
tolerated with no ocular inflammation, no ocular or treatment-related adverse events, and no dose limiting toxicities. Early signals of functional vision improvement were observed, including an equivalent 12-letter gain in Best Corrected Visual
Acuity (BCVA) in the treated study eye. In addition, structural improvement in central subfield thickness (CST) was observed with a 23% decrease in the study eye. Resolution of intraretinal fluid was also seen as early as 1-month in areas with
less atrophy.
We are planning to discuss with the FDA an adaptive Phase 1/2/3 trial design, similar to the design of the OPGx-LCA5 trial, with
potential acceleration to a pivotal study.
Early-Stage Gene Therapy Programs
We also have five programs in pre-clinical development. Three programs are currently in IND-enabling studies, and several have received grant and/or partner funding to
support their development.
OPGx-RHO
Encoded by the RHO gene, rhodopsin is an important component of the photopigment in rod photoreceptors that absorbs light and provides structure to the rod outer segments.
Autosomal dominant mutations in rhodopsin cause RHO-adRP, which is characterized by progressive death of the rod photoreceptors that can lead to vision loss.
OPGx-RHO is a gene therapy that targets autosomal dominant retinitis pigmentosa caused by RHO mutations (RHO-adRP). RHO-adRP affects approximately 8,800 people in the U.S.,
and 30,580 people worldwide, making it one of the most common IRDs.
OPGx-RHO is designed to preserve the rod photoreceptors by replacing a patient’s mutant RHO gene with a functional copy, addressing the underlying genetic cause of disease.
The program is currently in preclinical development and is being co-funded by the Foundation Fighting Blindness (“FFB”) and the National Institutes of Health (“NIH”).
OPGx-RDH12
Retinal dehydrogenase (RDH12)-associated disease is a severe, early-onset IRD marked by visual acuity loss in early childhood and rapid progression during adolescence.
Patients with RDH12 mutations, which affect approximately 2,500 people in the U.S. and 31,040 people worldwide, often have early visual acuity loss with retinal structural changes by two years of age, and longitudinal studies have reported a
steep decline in visual acuity within the second decade of life. RDH12 encodes a retinol dehydrogenase enzyme involved in the visual cycle, protecting photoreceptors from toxic metabolite accumulation.
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OPGx-RDH12 is designed to restore protein expression and halt functional deterioration in patients with retinal dystrophy caused by mutations in the RDH12 gene. OPGx-RDH12
leverages AAVs to transport a functional gene to photoreceptors in the retina. In preclinical studies of OPGx-RDH12 in cellular and mouse models, we observed evidence of functional improvement of RDH12 activity. The program is currently in
preclinical development and is being co-funded by the Global RDH12 Alliance.
OPGx-MERTK
MERTK-related IRD is a rare, autosomal recessive retinal dystrophy caused by mutations in the MERTK gene, leading to severe,
progressive vision loss. MERTK plays a critical role in phagocytosis of photoreceptor outer segments by RPE cells. Mutations in the MERTK gene impair the retina’s ability to recycle photoreceptor components causing a rod-cone dystrophy with
early macular atrophy, with retinitis pigmentosa being the most common phenotype. MERTK affects approximately 2,600 people in the U.S. and 22,000 people worldwide. There are currently no approved treatments for MERTK-related retinitis
pigmentosa.
OPGx-MERTK is being developed for retinal degeneration caused by mutations in the MERTK gene. The therapy is designed to deliver a functional copy of the MERTK gene to
retinal cells. We are advancing OPGx-MERTK using a modern AAV vector design, building on prior preclinical proof of concept and earlier clinical experience, with the aim of improving durability and efficacy. OPGx-MERTK is being co-funded by the
FFB Retinal Degeneration Fund.
In January 2026, we announced the launch and funding of a clinical trial for OPGx-MERTK in Abu Dhabi in collaboration with the Department of Health – Abu Dhabi (DoH), the
Cleveland Clinic Abu Dhabi, the Innovative Research Oversight and Support (IROS) division of the M42 group, and the Authority of Social Contribution – Ma’an. Clinical development activities are expected to commence at Cleveland Clinic Abu Dhabi
in 2026.
OPGx-NMNAT1
NMNAT1 is an enzyme essential for regenerating an essential metabolite, nicotinamide adenine dinucleotide (NAD+), in cell nuclei. Photoreceptors, in particular, are highly
vulnerable to loss of NMNAT1 function.
OPGx-NMNAT1 is a gene augmentation therapy designed to halt functional deterioration
in pediatric patients with retinal degenerative disease caused by mutations in the nicotinamide mononucleotide adenylyltransferase 1 (NMNAT1) gene, which affects approximately 1,200 people in the U.S. and 5,290 people worldwide. Preclinical
data in a mouse model that recapitulate key features of the human disease demonstrated that AAV-mediated delivery of NMNAT1 stabilized retinal degeneration. The program is currently in preclinical development.
OPGx-CNGB1
CNGB1-related eye disease is an autosomal recessive form of retinitis pigmentosa caused by mutations in the CNGB1 gene, which encodes a subunit of the rod photoreceptor
cyclic nucleotide-gated (CNG) ion channel. It typically presents with childhood-onset night blindness, slowly progressive visual field loss, and relatively preserved central visual acuity until later stages. CNGB1 affects approximately 2,100
people in the U.S. and 10,150 people worldwide.
OPGx-CNGB1 is an AAV gene therapy being developed for retinitis pigmentosa due to mutations in the CNGB1 gene.
Phentolamine Ophthalmic Solution 0.75% (PS)
In addition to gene therapies, our pipeline includes Phentolamine Ophthalmic Solution 0.75%, a small-molecular,
preservative-free ophthalmic therapy being developed to address multiple common and underserved vision conditions. PS is FDA-approved for pharmacologically induced mydriasis. Our objective with our clinical development programs for PS is to
provide a safe, long-lasting and effective solution that restores near vision and enhances overall visual performance for people with presbyopia and low-light visual disturbances following keratorefractive surgery. To date, PS has shown a
favorable tolerability profile with minimal to no headaches or dimming, and no drug-related increase in risk of retinal detachment, retinal tears, or vitreofoveal traction.
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License and Collaboration
In November 2022, we entered into a license and collaboration agreement (the “Viatris License Agreement”) with a company now known as Viatris, Inc. (“Viatris”), pursuant to
which we granted Viatris an exclusive license to intellectual property used to develop, manufacture, import, export and commercialize worldwide, except for certain countries and jurisdictions in Asia (i) our refractive product candidate PS, and
(ii) PS with low dose pilocarpine for treating presbyopia.
The license rights for PS include three potential indications (a) reversal of pharmacologically-induced mydriasis, (b) presbyopia, and (c) decreased vision under mesopic
(low) light conditions after keratorefractive surgery.
Mechanism of Action
PS is a once-daily sterile eye drop formulation of phentolamine mesylate designed to reduce pupil diameter and improve visual acuity. The active pharmaceutical ingredient
of PS, phentolamine mesylate, is a relatively non-selective alpha-1 and alpha-2 adrenergic antagonist that inhibits activation of the smooth muscle of the iris, reducing pupil diameter.
It works by blocking alpha-1 and receptors found on the radial iris dilator muscle, which are activated by the alpha-1 adrenergic receptors. PS is designed to reduce pupil
diameter through a sympatholytic mechanism of action that avoids engaging the ciliary muscle, potentially reducing risks such as retinal tears or detachment associated with older parasympathomimetic agents. This differentiated mechanism allows
potential improvement in visual performance while preserving distance vision, accommodation, and contrast sensitivity.
For the treatment of pharmacologically-induced mydriasis, PS, either by directly antagonizing the alpha-1 agonist or by indirectly antagonizing the pupil dilation effect of
muscarinic blocking, may expedite the reversal of mydriasis prior to natural reversal. For presbyopic patients, we believe that it is possible to reach a target 2 mm to 3 mm optimal pupil diameter by relaxing the dilator iris muscle with PS and
contracting the iris sphincter muscle with a muscarinic agonist such as low dose pilocarpine. Lastly, for the dim light vision disturbances, it is proposed that a moderate miotic effect by application of PS might mitigate night vision
difficulties, a large portion of which are caused by imperfections or aberrations present in the periphery of the cornea.
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Pupillary Mechanism:
Clinical Development Process and Plan
PS has been assessed in 14 investigator-initiated and company-sponsored Phase 1, Phase 2, and Phase 3 clinical trials. Across all these trials, over 1,200 adult subjects
have been exposed to at least one dose of phentolamine ophthalmic solution 0.75%. Clinical trial data from Phase 2 and Phase 3 trials have been presented at meetings of the American Academy of Ophthalmology (AAO), Association for Research in
Vision and Ophthalmology (ARVO), and American Society of Cataract and Refractive Surgery (ASCRS) and may be presented at future medical conferences.
Pharmacologically Induced Mydriasis: RYZUMVI® (phentolamine ophthalmic solution) 0.75%
Pharmacologically induced mydriasis is the artificial dilation of the pupils caused by chemical substances, such as eye drops or medications, rather than natural light
changes. These substances work by blocking parasympathetic signals that constrict the pupil or stimulating sympathetic pathways that dilate it, resulting in pupils that are often fixed, unresponsive to light, and sometimes cause blurry vision.
There are approximately 100 million eye dilations in the United States performed annually.
In September 2023, PS was approved by the FDA for the treatment of pharmacologically
induced mydriasis produced by adrenergic agonists (e.g., phenylephrine) or parasympatholytic agents (e.g., tropicamide), or a combination thereof, under the brand name RYZUMVI® which triggered a $10 million milestone payment under the Viatris
License Agreement. RYZUMVI® was commercially launched by Viatris in April 2024.
Presbyopia: VEGA Program
Presbyopia is an ophthalmic disorder that involves the progressive loss of ability to focus on close objects that typically becomes noticeable in the early to mid-40s. As
the eye ages, the ability to focus for reading and other tasks that require clear vision at near distances decreases. Presbyopia patients experience blurred near vision, difficulty seeing in dim light and eye strain. This ubiquitous condition
leads to the widespread use of reading glasses or bifocals. It is estimated that 128 million Americans, and approximately 2 billion people worldwide, have presbyopia, and this number is expected to grow as the population ages. PS is being
developed as a non-invasive, once-daily alternative to reading glasses or multifocal lenses. The program has completed two pivotal Phase 3 trials.
In June 2021, we announced positive results from VEGA-1, our Phase 2 trial evaluating PS for the treatment of presbyopia. VEGA-1 (NYXP-201) was a double-masked, randomized,
placebo-controlled, multi-center trial of PS and LDP compared with vehicle (placebo) ophthalmic solution in presbyopic patients. A total of 150 patients were randomized 4:3:3:4 to one of four treatment groups. The primary efficacy endpoint for
this study was met.
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Opus Genetics, Inc.
Form 10-K
In November 2023, we announced positive results from VEGA-2, our first Phase 3 trial evaluating PS for the treatment of presbyopia. VEGA-2 (NYXP-301) is a double-masked,
randomized, placebo-controlled multi-center trial of PS, placebo and with adjunctive LDP compared with vehicle (placebo) in presbyopic patients. 333 subjects were randomized 1:1:1:1 to one of four treatment groups in two stages. The primary
efficacy endpoint was met.
In June 2025, we announced positive topline results from VEGA-3, our second pivotal Phase 3 trial evaluating PS for the treatment of presbyopia. The study met its primary
and key secondary endpoints, demonstrating rapid and sustained improvement in near visual acuity with a favorable safety profile and no evidence of tachyphylaxis over six weeks.
VEGA-3 was a multicenter, randomized, double-masked, placebo-controlled Phase 3 study that enrolled 569 participants across 36 sites in the United States. Subjects were
randomized in a 3:2 ratio to receive either PS or placebo, administered once daily in the evening. The VEGA-3 trial met its primary endpoint, with a statistically significant 27.2% of participants treated with PS achieving a ≥15-letter
improvement in binocular distance-corrected near visual acuity (DCNVA), with less than a 5-letter loss in binocular best-corrected distance visual acuity (BCDVA) at 12 hours post-dose on Day 8, compared to 11.5% of patients on placebo
(p<0.0001). The trial also met key secondary efficacy endpoints, reinforcing the benefit observed.
Based on positive results from both Phase 3 studies, Viatris, the Company’s global commercialization partner for PS, filed a supplemental New Drug Application (sNDA) with
the FDA in December 2025. In February 2026, the FDA accepted the sNDA and set a Prescription Drug User Fee Act (PDUFA) action date of October 17, 2026.
Decreased Vision Under Dim (Mesopic or Low) Light Conditions After Keratorefractive Surgery: LYNX Program
Phentolamine Ophthalmic Solution 0.75% is also being developed for visual disturbances under mesopic, or low-light conditions following keratorefractive surgery, including
Laser-Assisted In Situ Keratomileusis (LASIK), Photorefractive Keratectomy (PRK), Small-Incision Lenticule Extraction (SMILE) and Radial Keratotomy (RK). These patients may experience glare, halos, starbursts, and impaired night driving, and
there are currently no FDA-approved treatments. There are an estimated 600,000 to 700,000 laser vision correction procedures conducted every year in the U.S., of these, 35% of LASIK patients report dim light disturbances post treatment.
In December 2023, we entered into an agreement under a Special Protocol Assessment (SPA) with the FDA for PS for decreased vision under dim (mesopic or low) light
conditions following keratorefractive surgery. We have also received Fast Track designation from the FDA in this indication.
LYNX-1 (NYXDLD-301) was a Phase 3 double-masked, randomized, placebo-controlled, multi-center study comparing PS to placebo ophthalmic solution in 145 patients experiencing
dim light vision disturbances at multiple sites across the U.S. Treatment was self-administered in each eye once daily at or near bedtime for 14 days. PS met the primary endpoint, showing a statistically significant higher percentage of
subjects with ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (≥ 3 lines) of improvement compared to baseline in monocular mLCVA at Day 8. A total of 66 Treatment Emergent Adverse Events (“TEAEs”) were reported in 23 subjects
(32%) treated with PS and 22 TEAEs were reported in 12 subjects (16%) treated with placebo. All TEAEs were mild or moderate in intensity, except for one severe TEAE (instillation site pain) experienced by a subject in the PS group. No subjects
had any TEAEs leading to withdrawal from the study. One subject in each treatment group (PS and placebo) had TEAEs leading to study medication discontinuation.
In June 2025, we announced positive topline results from LYNX-2, our first pivotal Phase 3 trial evaluating PS for the treatment of significant, chronic night driving
impairment in keratorefractive patients with reduced mesopic vision. The LYNX-2 study met its primary endpoint of a gain of three lines (or 15 letters) or more of distance vision improvement on a low contrast chart in low light conditions after
15 days of dosing. In the study, 17.3% of patients treated with Phentolamine Ophthalmic Solution 0.75% achieved a ≥15-letter Early Treatment Diabetic Retinopathy Study (ETDRS) (≥ 3-line) improvement in Mesopic Low Contrast Distance Visual
Acuity (mLCVA) at Day 15, compared to 9.2% in the placebo group (p<0.05).
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Form 10-K
In September 2025, we announced that the first patient was dosed in LYNX-3, our
second pivotal Phase 3 clinical trial evaluating PS for the treatment of significant, chronic night driving impairment in keratorefractive patients with reduced mesopic vision. Topline results from LYNX-3 are expected in the first half of
2026.
APX3330
Mechanism of Action
APX3330 is a selective small molecule that is designed to act on the dual-functioning Apurinic/Apyrimidinic Endonuclease 1/Redox Effector Factor-1 (APE1/Ref-1) protein,
referred to as Ref-1. This protein is implicated in both redox signaling and DNA repair. Because APX3330 selectively inhibits the redox function without affecting the molecule’s ability to carry out DNA repair, normal cell function is left
intact. Moreover, interference of Ref-1 activity with APX3330 blocks angiogenesis and inflammation by simultaneously decreasing the activity of several important transcription factors such as HIF-1α and NF-κB (see the below figure for a visual
description). HIF-1α regulates the expression of VEGF, a protein that is paramount for angiogenesis, and NF-κB is an upstream regulator of proteins involved in inflammatory processes such as TNFα and chemokines.
APX3330 has a dual mechanism that decreases both abnormal angiogenesis and inflammation. APX3330 blocks pathways downstream of Ref-1. Blocking HIF-1α reduces VEGF
signaling, and blocking NF-κB modulates VEGF, TNF-α and other inflammatory cytokine production. In contrast, anti-VEGF agents solely inhibit the actions of VEGF.
Clinical Development Process and Plan
APX3330 has been studied in over 375 healthy volunteers or patients with hepatitis or cancer or diabetic retinopathy (DR).
In August 2022 we completed ZETA-1, a Phase 2b double-masked, randomized, placebo-controlled, multi-center trial in 103 patients with DR and diabetic macular edema (DME).
This study evaluated the effect of 600 mg daily dose of APX3330 in treating patients with DR, including moderately severe Nonproliferative Diabetic Retinopathy (NPDR) to mild Proliferative Diabetic Retinopathy (PDR), as well as patients with
DME without loss of central vision. The primary endpoint was percent of patients with a ≥2 step improvement in Early Treatment of Diabetic Retinopathy Study (ETDRS) diabetic retinopathy severity scale (DRSS) at week 24 in the study eye. The
ZETA-1 trial did not meet the primary endpoint in the study eye; however, the trial provided evidence of the potential for clinically meaningful prevention of progression of diabetic retinopathy when evaluating both eyes. In the ZETA-1 trial,
13% of subjects within the placebo arm compared to 5% of subjects within the APX3330 arm worsened by ≥ 3 step on binocular person-level scale from baseline at week 24. Additional efficacy endpoints were directionally supportive of the
biological effect of APX3330 in slowing the progression of DR and preserving vision.
In the first half of 2024, we conducted a subset analysis for ZETA-1 to evaluate the efficacy of APX3330 in slowing DR progression using the FDA’s agreed upon registration
endpoint of a 3-step change on a binocular diabetic Retinopathy Severity Scale (DRSS). This 17-step person-level scale accounts for the DRSS scores of the two eyes and then anchors the step to the worse eye. The subset comprised 68 participants
from the ZETA-1 trial who had a baseline DRSS score of 47 or 53 in at least one eye and 43, 47 or 53 in the other eye. Analysis of the ZETA-1 Phase 2 subset using the binocular person-level scale showed that no participants in the APX3330 group
had a ≥ 4-step worsening at week 24 compared to 15.2% in the placebo group, representing a 100% reduction between groups (p=0.07). Similarly, only 5.7% of APX3330-treated subjects had a ≥ 3-step worsening at week 24 compared to 15.2% of placebo
subjects, representing a 62.5% reduction between groups (p=0.26). Fewer participants in the APX3330 group developed proliferative diabetic retinopathy (PDR) by week 24 compared to the placebo group (11% vs 26% respectively; p=0.13).
Overall, there were 211 adverse events (“AEs”) in 64 subjects, with only 31 of these AEs considered drug-related (14 APX3330, 17 placebo). All treatment-related AEs were
mild or moderate in severity. There were no adverse treatment effects on any other characteristics of the ophthalmic examination or on any assessments of systemic safety.
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In October 2023, we conducted an EOP2 meeting with the FDA and shared the outcome of the meeting in October 2023 which stated the agreement on the
registrational program for APX3330, including confirmation of the primary endpoint for registration of a systemic agent for DR. In December 2024, the Company reached agreement with the FDA under SPA related to a Phase 3 clinical trial design.
However, due to our current strategic focus on advancing our gene therapy candidates, we are seeking a strategic partner to advance the clinical development of this late-stage diabetic retinopathy program
Overview of Eye Disease Market
Inherited Retinal Disease Market
Retinal degeneration is a devastating cause of severe vision loss beginning in childhood and progressing into adulthood. There are more than 350 genes known to cause
inherited retinal diseases. Only one of these, RPE65, has an approved treatment, LUXTURNA®. Many of the mutations attributable to IRDs may be amenable to gene augmentation therapy using an established, standardized subretinal delivery method.
Our pipeline addresses seven of these mutations with variable prevalence as a potential one-time treatment.
The prevalence of IRDs varies widely across regions, creating significant opportunities for therapeutic development in both
U.S. and ex‐U.S. markets. The IRD prevalence estimates highlight the distribution of genetically defined patient populations by region and gene, underscoring the breadth of our addressable market.
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Anterior (Front of the Eye) Segment Disease Market
There are approximately 100 million eye dilations in the United States and this number is expected to go up with the increasing aging and diabetic population that requires
more frequent eye exams and procedures. Millions of Americans also suffer from various refractive errors in addition to an age-related loss in accommodation known as presbyopia.
Presbyopia is common in patients over the age of 40 years, which results in decreased ability to see objects at near distances due to a loss of accommodative function. This
condition affects nearly 133 million Americans and usually requires reading glasses, bifocals/varifocals, contact lenses or surgical refractive treatment to enable clear vision at near distances.
Further, according to GlobalData, approximately 38 million patients in the U.S. suffer from dim light or night vision disturbances caused by LASIK, night myopia,
keratoconus, eye surgery, or the natural aging process. There is also a global trend in vision disturbances in younger individuals due to the overuse of smartphone screens. There are 600,000 to 700,000 laser vision correction procedures
conducted every year in the U.S., of these, 35% of LASIK patients report dim light disturbances post treatment.
Sales and Marketing
In November 2022, we entered into the Viatris License Agreement for the development and commercialization of all PS indications in the U.S. and ex-U.S. markets (excluding
certain countries in Asia). Viatris is responsible for any commercialization activities associated with any approved PS indications.
Currently, we do not have any employees dedicated to the sales and marketing of any of our pipeline products. We may look to build our own sales and marketing
infrastructure or pursue a partnership to commercialize any future drugs upon approval.
Manufacturing
We contract with manufacturers to produce drug substances (chemical and biologic), gene therapies drug products, and formulated drug products for use in our preclinical
studies and clinical trials, utilizing reliable and reproducible processes and common manufacturing techniques which are consistent with applicable regulations for the intended use. Gene therapy drug products, Master Cell Banks, and plasmids
are located at a contracted biorepository for long term storage, or the manufacturing site prior to relocation for storage. Contracts for ongoing stability storage and testing are established for current clinical inventory of drug substances,
gene therapies, and drug products. We do not have any long-term manufacturing agreements but do intend to secure such arrangements for drug substances, gene therapies, or drug products in the event any of our products being developed become
commercialized. We do not currently own or operate, and we have no current plans to establish any manufacturing facilities.
OPGx-LCA5
The manufacturing of current Good Manufacturing Practice (“cGMP”) -grade OPGx-LCA5 drug substance and drug product for nonclinical toxicology and clinical studies was
performed at an academic manufacturing partner, using an adherent process, with in-house and outsourced testing. The current batch size is 50 liters.
The technical transfer of the manufacturing process for drug substance and drug product to a cGMP commercial contract drug manufacturing organization (“CDMO”), SAFC
Carlsbad Inc., is ongoing. The new process includes a suspension process at 50L scale including analytical support, for pivotal Phase 3 clinical and pre-commercial readiness and Product Process Qualification (PPQ).
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OPGx-BEST1
Manufacturing of cGMP-grade OPGx-BEST1 drug substance and drug product for BEST1 nonclinical toxicology and clinical studies was performed at Catalent Incorporated, with
in-house and outsourced testing. Process and analytical development work for OPGx-BEST1 were conducted at small scale. Following scale-up, replicate batches were produced at 200L scale, using the same process used for the Good Laboratory
Practice (“GLP”) toxicology studies. Batches of drug product, drug substance, and diluent were placed on stability programs which remain ongoing.
The technical transfer of the manufacturing process for drug substance and drug product to a cGMP CDMO, SAFC Carlsbad Inc., is ongoing. The new process includes a
suspension process at 200L scale including analytical support, for pivotal Phase 3 clinical and pre-commercial readiness and PPQ.
Early-Stage Gene Therapy Assets
The remaining IRD pipeline, including OPGx-RHO, OPGx-RDH12, OPGx-MERTK, OPGx-NMNAT1, and OPGx-CNGB1, are pre-clinical candidates in varying stages of phase appropriate
development, based on the asset. Manufacturing completed to date has been conducted to support non-clinical toxicology programs, at a scale of 50L or less, with planning to support technical transfer and scale-up ongoing. There are no current
or ongoing manufacturing agreements in place. A request for proposal process, to include small scale process development, technical transfer, and analytical method development, to identify a manufacturing partner is being conducted. The
overall corporate strategy is to advance each from the current manufacturing status, from pre-clinical into clinical Phase 1/2 readiness consolidated with a CDMO meeting capability requirements under cGMP manufacturing conditions.
Phentolamine Ophthalmic Solution 0.75% (PS)
Pursuant to the Viatris License Agreement, we have transferred commercial manufacturing
responsibilities for RYZUMVI® to Viatris. Transfer of commercial manufacturing responsibilities for additional indications for which PS is in development is intended. Currently, we use purchase orders with multiple manufacturers for PS
clinical supply manufacturing. We are qualifying our selected manufacturers to provide bulk drug substances and drug products in conjunction with the planned sNDA regulatory submissions to the FDA.
APX3330
APX3330 is a solid oral formulation of a small molecule drug substance that is synthesized from readily available raw materials and using conventional chemical processes.
The APX3330 drug substance has been optimized to a new form. Process and analytical development of APX3330 drug substance and drug product is in development, and plans for production scale up according to cGMP regulatory requirements are
established. Previously, the APX3330 drug product manufacturer performed pharmaceutical development to support the cGMP manufacturing campaign for tablets of 60 mg and 120 mg dose strengths, the latter being used in prior clinical trials. We
have reformulated the drug product and increased the dose strength to 300 mg for convenient once or twice a day dosing and completed one human bioavailability trial with the new formulation to demonstrate comparability with the prior
investigational product. Planning to complete the remaining process development, scale up, and validation are established, pending execution following a partnership agreement.
Collaborations and Licenses
Viatris License Agreement
In November 2022, the Company entered into the Viatris License Agreement, pursuant to which it granted Viatris (as successor to Famy) an exclusive, perpetual,
sub-licensable license to develop, manufacture, import, export and commercialize (i) PS, for treating (a) reversal of mydriasis, (b) night vision disturbances or dim light vision, and (c) presbyopia, and (ii) PS and low dose pilocarpine for
treating presbyopia (together, the “PS Products”) worldwide except for certain countries and jurisdictions in Asia (the “Viatris Territory”). The Company retains the exclusive right to develop, manufacture, have manufactured, import, export and
commercialize the PS Products outside of the Viatris Territory.
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Under the terms of the Viatris License Agreement, the Company, in partnership with Viatris, will develop the PS Products in the United States. Viatris will reimburse the
Company for agreed-to budgeted costs related to the development of the PS Products through FDA approval, and then share costs above the agreed upon threshold amount.
Pursuant to the Viatris License Agreement, the Company received a one-time non-refundable cash payment of $35 million in November 2022 for the exclusive, perpetual,
sub-licensable license to develop, manufacture, import, export and commercialize the PS Products in the Viatris Territory. In addition, with respect to the PS Products, the Company will be eligible to receive potential additional payments of up
to $130 million upon achieving certain specified regulatory or net sales milestones, with the first milestone payment of $10 million already made following approval by the FDA of PS for reversal of mydriasis, which occurred during the third
quarter of 2023. The Company will also receive tiered royalties, starting at low double-digit royalties up to low 20% royalties, based on the aggregate annual net sales of all PS Products in the United States, and will receive low double-digit
royalties based on all annual net sales in the Viatris Territory outside of the United States. The royalty payments will continue on a country-by-country basis from the date of the first commercial sale of the first PS Product in a country of
the Viatris Territory until December 31, 2040.
University of Pennsylvania LCA5/RDH12 License Agreement
On June 15, 2022, Opus entered into an amended and restated license agreement (the “LCA5/RDH12 Agreement”) with the Trustees of the University of Pennsylvania (“Penn”)
pursuant to which it was granted an exclusive, royalty-bearing license to certain patents and a non-exclusive license to certain information relating to products directed towards treatment or correction of mutation of the LCA5 or RDH12 genes.
In connection with signing, we granted to Penn shares of common stock equal to a mid single-digit percentage of our then total capital stock calculated on a fully diluted basis. We will make additional payments to Penn upon the achievement of
certain specified development, regulatory and commercial milestone events up to a maximum potential aggregate amount of $2.6 million. Until we are required to pay royalties under the LCA5/RDH2 Agreement, we must pay an annual license
maintenance fee to Penn in the low tens of thousands of dollars. In addition, we will make quarterly tiered royalty payments in low single-digit percentages on net sales of licensed products, subject to minimum annual royalty payments up to the
low tens of thousands of dollars, depending on the given year. We will also make payments on any sublicense income, in percentages up to the mid teens, with such percentage depending on the stage of product development. The term of the
LCA5/RDH12 Agreement continues until the later of (i) expiration of the licensed patents and (ii) 10 years after first commercial sale, unless Penn has cause to terminate earlier for our material breach of the license or bankruptcy. We have the
right to terminate the LCA5/RDH12 Agreement at any time during the term with certain prior written notice to Penn.
Iveric Asset Purchase Agreement – BEST1 and RHO Programs
On December 23, 2022, Opus entered into an asset purchase agreement with Iveric (the “Iveric Agreement”) pursuant to which the Company acquired certain assets, including
the BEST1 License (as defined below), relating to the BEST1 and RHO products.
If, with respect to the BEST1 products or the RHO products during a specified earn-out period (i.e., from the date of signing the Iveric Agreement until the later of 15
years following first commercial sale of a product in a country or the expiration of all applicable regulatory exclusivity periods with respect to such product in such country), (i) we materially breach our diligence obligations with respect to
the BEST1 products or the RHO products, as applicable, (ii) the acquired intellectual property licenses relating to the BEST1 products or the RHO products, as applicable, are terminated for any reason, or (iii) we cease efforts to exploit the
BEST1 products or the RHO products, as applicable, for a certain period (subject to certain exceptions), then upon Iveric’s request we are obligated to assign to Iveric our rights to the BEST1 products or the RHO products, as applicable,
including related patent rights, contracts, information and regulatory documents.
Until the sixth anniversary of signing, Iveric has a right of first refusal if we intend to seek or pursue a deal to license, sell, transfer or otherwise dispose of all or
substantially all of our assets primarily relating to either or both of the BEST1 or RHO product candidates, or if we receive an unsolicited offer from a third party relating to the foregoing.
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In connection with signing of the Iveric Agreement, we paid Iveric an upfront fee of $500,000 and issued to Iveric certain shares of series seed preferred stock of Opus
equivalent to a high single digit percentage of our then outstanding capital stock. We will make additional payments to Iveric upon the achievement of specified (i) development milestones, the maximum potential aggregate amount of such
milestones being $11.35 million with respect to the BEST1 program and $1.45 million with respect to the RHO program and (ii) commercial milestones, the maximum potential aggregate amount of such milestones being $95.4 million with respect to
the BEST1 program and $3.5 million with respect to the RHO program. In addition, we will make royalty payments in the low single digit percentages on net sales of licensed RHO and BEST1 products.
Penn and University of Florida BEST1 License Agreement
On April 10, 2019, Iveric entered into an exclusive patent license agreement (as amended, the “BEST1 License”) with Penn and the University of Florida Research Foundation
(“UF”), which agreement was assigned to Opus under the terms of the Iveric Agreement. Under the BEST1 License, Opus received exclusive patent rights and non-exclusive knowhow and data rights with regard to products to treat diseases associated
with mutations in the BEST1 gene. In connection with signing, Iveric paid Penn an upfront fee in the low hundreds of thousands of dollars. We will make additional payments to Penn upon the achievement of specified (i) clinical and regulatory
milestones up to a maximum potential aggregate amount of $15.65 million for the first licensed product, regardless of category (i.e., “wildtype only products” or “knockdown and replace products”), and $3.13 million for the first licensed
product from a different category, and (ii) commercial milestones, up to a maximum potential aggregate amount of $48 million for the first licensed product, regardless of category, and $9.6 million for the first licensed product from a
different category. In consideration for Penn and UF’s consent to the assignment of the BEST1 License to us under the Iveric Agreement, we will also pay Penn a percentage, in the mid teens, of each milestone payment that we are required to pay
to Iveric under the Iveric Agreement. Until we are required to pay royalties under the BEST1 License, we must pay an annual license maintenance fee to UF and Penn in the low tens of thousands of dollars. In addition, we will make quarterly
tiered royalty payments in the low single-digit percentages on net sales of licensed BEST1 products, subject to minimum annual royalty payments in the mid tens of thousands of dollars, starting from the earlier of the first commercial sale of a
licensed product or a future specified date. We will also make payments on sublicense income, in percentages up to the mid teens, with such percentage depending on the stage of product development.
The term of the BEST1 License continues until the later of (i) expiration of the licensed patents, (ii) expiration of regulatory exclusivity, or (iii) 10 years after the
first commercial sale of a licensed product, unless UF or Penn has caused the BEST1 License to terminate earlier for our material breach of the license or bankruptcy. We have the right to terminate the BEST1 License in its entirety or with
respect to a particular category of licensed products with certain prior written notice to Penn (without affecting our rights or obligations to the other category of licensed products), at any time prior to an investigational new drug
application or clinical trial application (“IND”) for a licensed product in such category becoming effective. After an IND for a licensed product in a particular category becomes effective, then the BEST1 License will be non-cancellable with
respect to such category, except that we will have the right to terminate the agreement with respect to such category by providing UF and Penn written notice.
LCA5 VR License
On March 2, 2023, Opus entered into a non-exclusive license agreement (the “LCA5 VR License”) with Penn pursuant to which it was granted a non-exclusive license to certain
patents and copyrights relating to testing visual function using simulated living situations in individuals with visual disorders, for Opus’ use in clinical trials for the evaluation of retinal disorder treatments caused by LCA5 mutations. In
connection with signing, we paid Penn an upfront fee in the low tens of thousands of dollars. We will make additional payments to Penn, in the low single digit thousands of dollars, for each use of a licensed product in a clinical trial. The
term of the LCA5 VR License continues until six months after the conclusion of all clinical trials for the evaluation of treatments for retinal disorders caused by a mutation or mutations in the LCA5 gene. We have the right to terminate the
LCA5 VR License at any time during the term with certain prior written notice to Penn.
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Penn and UF RHO License Agreement
On June 6, 2018, Iveric entered into an exclusive patent license agreement (the “RHO License”) by and between Penn and UF pursuant to which the Company has exclusive patent
rights and non-exclusive knowhow and data rights with regard to products to treat rhodopsin-mediated diseases. In return for these rights, the Company is obligated to make certain development milestone payments and royalty payments on future
sales of such products.
Massachusetts Eye and Ear Infirmary License Agreement
On November 9, 2021, Opus entered into a license agreement (the “MEEI License”) with the Massachusetts Eye and Ear Infirmary (“MEEI”), granting an exclusive worldwide
license of MEEI patents for use in the NMNAT1 program for all products and processes including the treatment of retinal disease in humans, and a non-exclusive worldwide license to technological information. In return for these rights, the
Company is obligated to make certain development milestone payments and royalty payments on future sales of such products.
Apexian Sublicense Agreement
On January 21, 2020, the Company entered into a sublicense agreement with Apexian Pharmaceuticals, Inc. pursuant to which it obtained an exclusive worldwide patent and
other intellectual property rights relating to a Ref-1 Inhibitor program, including APX3330, for the treatment of ophthalmic or diabetic diseases. In exchange for the patent and other intellectual rights, the Company agreed to certain milestone
payments and royalty payments on future sales.
Intellectual Property
Gene Therapy
We in-license multiple patents and patent applications directed to our gene therapy programs. We also own one patent family directed to our MERTK therapeutic program. Our
patent estate for each gene therapy program, as of December 31, 2025, is described in more detail below.
For our LCA5 therapeutic program, we in-license one patent family directed to compositions of matter and therapeutic methods using such compositions of matter. The patent
family contains patents in the U.S., Japan, Australia, and South Korea and pending patent applications in the U.S., Europe, and additional foreign countries. The foregoing U.S. patent expires in 2039, and the Japanese, Australian, and South
Korean patents, including any patents that may be granted based on the foregoing pending patent applications, will expire in 2038, each not including any patent term extension.
For our BEST1 therapeutic program, we in-license four patent families. The first patent family is directed to compositions
of matter and therapeutic methods using such compositions of matter and has one patent in China and patent applications pending in the U.S., Europe, Japan, and additional foreign countries. The patent in China, and patents if granted based
on the foregoing patent applications, would expire in 2039, not including any patent term extension. The second and third patent families are each directed to methods of treatment and have patent applications pending in the U.S., Europe,
Japan, and additional foreign countries. Patents, if granted based on the foregoing patent applications, would expire in 2041, not including any patent term extension. The fourth patent family is direct to methods of treatment and methods
for assessing treatment and has patent applications pending in the U.S. and Europe. Patents, if granted based on the foregoing patent applications, would expire in 2042, not including any patent term extension.
For our RHO therapeutic program, we in-license two patent families, each directed to compositions of matter and therapeutic methods using such compositions of matter. The first patent family
has patents in the U.S., Europe, Japan, and additional foreign countries, while the second patent family has patents in the U.S., Japan and China. Each patent family also has patent applications pending in the U.S., Europe, and additional
foreign countries. The foregoing patents, including any patents to grant based on the foregoing patent applications, will expire from 2037 to 2042, not including any patent term extension.
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For our MERTK therapeutic program, we own one patent family directed to compositions of matter and therapeutic methods
using such compositions of matter. This patent family contains pending patent applications in the US., Europe, Japan, and additional foreign countries. Patents, if granted based on the foregoing patent applications, would expire in 2044,
not including any patent term extension.
For our RDH12 therapeutic program, we in-license one patent family directed to compositions of matter and therapeutic methods using such compositions of matter, consisting
of patents in the U.S., Japan, Australia, and additional foreign countries and pending patent applications in the U.S., Europe, and additional foreign countries. The foregoing patents, including any patents to grant based on the pending patent
applications, will expire in 2037, not including any patent term extension.
For our NMNAT1 therapeutic program, we in-license one patent family directed to compositions of matter and therapeutic methods using such compositions of matter, consisting
of one U.S. patent and pending patent applications in the U.S., Europe, Japan, and additional foreign countries. These patents, if granted based on the pending patent applications, would expire in 2041, not including any patent term extension.
For our CNGB1 therapeutic program, we in-license one patent family directed to compositions of matter and therapeutic methods using such compositions of matter. This
patent family contains a patent in the U.S. and Japan and pending patent applications in the U.S., Europe, and additional foreign countries, whereby the U.S. and Japanese patents and patents, if granted, based on the foregoing pending patent
applications, expire in year 2038, not including any patent term extension.
PS
Our patent estate includes patents and patent applications to forms of phentolamine mesylate, formulations containing phentolamine mesylate, methods of using phentolamine
mesylate, and methods of manufacturing phentolamine mesylate. We own all of the worldwide rights to PS for all indications, but out-license certain rights to PS pursuant to the Viatris License Agreement.
Our patent estate relating to PS contains over 15 U.S. patents, over nine pending U.S. non-provisional patent applications, two pending international patent application, as well as issued
patents in Australia, Canada, Europe, Japan, and Mexico and pending patent applications in Europe, Japan, and other foreign countries. Multiple U.S. patents and counterpart Australian, Canadian, European, and Japanese patents are directed to
aqueous phentolamine mesylate formulations and are scheduled to expire in 2034. Additional multiple U.S. patents and counterpart Australian, Canadian, European, and Japanese patents are directed to methods of improving visual performance
using, for example, phentolamine mesylate and are scheduled to expire in 2034.
We also own two U.S. patents with claims to methods of treating presbyopia, and three U.S. patents with claims to methods of treating mydriasis—each of the foregoing U.S. patents are
scheduled to expire in 2039. Additionally, we own one pending U.S. patent application with claims to treating presbyopia and two pending U.S. patent applications with claims to treating mydriasis. Counterpart patent applications are pending
in Europe, Japan, and other foreign countries—if granted based on these pending applications, these patents would expire in 2039. Patent applications are also pending in the U.S., Europe, Japan, and other foreign countries directed to
additional methods for treating mydriasis—if granted based on the foregoing patent applications, these patents would expire in 2042. We own two U.S. provisional patent applications directed to methods of treating presbyopia, whereby patents,
if granted based on non-provisional patent applications to be filed based on these provisional patent applications, would expire in 2046. In addition, we own a pending international patent application directed to improving visual performance
under low light conditions, whereby patents, if granted based on non-provisional patent applications to be filed based on this international patent application, would expire in 2045.
We also own two U.S. patents, one pending U.S. patent application, and pending foreign patent applications in Europe, Japan, and additional foreign countries directed to high-purity
phentolamine mesylate and methods for making the same. We also have a pending international patent application and pending U.S. patent application directed to particular phentolamine mesylate crystal forms and their use—if granted based on
the foregoing patent applications, these patents would expire in 2043.
We have obtained registration of the “RYZUMVI®” trademark in the United States.
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Table of Contents
Opus Genetics, Inc.
Form 10-K
APX3330
As of December 31, 2025, the patent estate that we in-license for APX3330 and related compounds contains over nine U.S. patents as well as issued patents in Europe, Japan, and additional
foreign countries, and pending patent applications in Europe and Canada. The license is for the use and commercialization of APX3330 and related compounds covered by the subject patents and patent applications in the field of human health
uses for ophthalmic and diabetes mellitus indications.
One in-licensed U.S. patent is directed to methods of treating diabetic retinopathy and other diseases using, for example, APX3330, and is scheduled to expire in year 2030,
not including any patent term extension. Counterpart patents have issued in Europe, Japan, and additional foreign countries, which are scheduled to expire in year 2028. A separate in-licensed patent family directed to methods of treating wet
Age-Related Macular Degeneration and other diseases using, for example, APX2009 or APX2014, contains one U.S. patent and patents in Europe, Japan, and additional foreign countries, as well as a pending patent application in Canada—these
patents, including any patents to grant based on the pending patent applications, will expire in 2039. Additional in-licensed patents and patent applications are directed to methods of treating certain retinal diseases, combination therapy,
and/or derivatives of APX3330—these patents, including any patents to grant based on the foregoing pending patent applications, will expire from 2028 to 2038, not including any patent term extension.
In addition, as of December 31, 2025, we own one U.S. provisional patent application, two U.S. non-provisional patent
application, one international patent application, and patent applications in Europe, Japan, and additional foreign countries and directed to methods of treating diabetic retinal diseases using APX3330. Patents, if granted, based on the
foregoing patent applications, would expire from 2042 to 2045, not including any patent term extension. Additionally, we own pending patent applications in the U.S., Europe, Japan and other foreign countries directed to APX3330 salts and
esters—whereby patents, if granted based on the foregoing patent applications, would expire in 2043, not including any patent term extension. Also, we own a pending international patent application directed to formulations containing APX3330,
whereby patents, if granted based on non-provisional patent applications to be filed based on this international patent application, would expire in 2044, not including any patent term extension.
Competition
We and our development partners face competition from both branded and generic pharmaceutical companies as well as products that are currently in development. Many of these
companies have significantly greater financial and human resources and experience in drug development, R&D, and commercialization. These competitors compete with us in recruiting and retaining qualified scientific and management personnel,
establishing clinical trial sites and patient enrollment for clinical trials, and acquiring products, product candidates or other technologies complementary to our programs. Smaller and other early-stage companies may also prove to be
significant competitors if they choose to partner with large, established companies.
Inherited Retinal Diseases
While we are not currently aware of any direct competitors for our OPGx-LCA5 or OPGx-BEST1 gene therapy program, there are various companies developing gene therapies for
the treatment of IRDs, which may ultimately directly compete with us in the future. To our knowledge, there are no active IRD gene therapy programs in development for the treatment of LCA5, BEST1, NMNAT1, or MERTK genes. With respect to the