UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
For the Fiscal Year Ended December 31, 2024
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 28, 2024, the last business day of the
registrant’s most recently completed second fiscal quarter, based on the closing price on that date of $1.53, was approximately $38.7
million. As of March 27, 2025, there were 45,483,823 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 2025 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, 2024.
Opus Genetics, Inc.
Form 10-K
TABLE OF CONTENTS
PART I 5
ITEM 1. BUSINESS 5
ITEM 1A. RISK FACTORS 51
ITEM 1B. UNRESOLVED STAFF COMMENTS 95
ITEM 1C. CYBERSECURITY 95
ITEM 2. PROPERTIES 96
ITEM 3. LEGAL PROCEEDINGS 96
ITEM 4. MINE SAFETY DISCLOSURES 97
PART II
ITEM 6. [RESERVED] 98
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 112
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 112
ITEM 9A. CONTROLS AND PROCEDURES 112
ITEM 9B. OTHER INFORMATION 113
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 113
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 113
ITEM 11. EXECUTIVE COMPENSATION 114
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 114
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 114
2
Table of Contents
Opus Genetics, Inc.
Form 10-K
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 Opus Acquisition
Risks Related to the Development of Our Gene Therapy Products and Other Product Candidates
3
Table of Contents
Opus Genetics, Inc.
Form 10-K
Risks Related to the Commercialization of RYZUMVI and Other Product Candidates
Risks Related to Our Financial Position and Need for Additional Capital
Risks Related to Government Regulation
Risks Related to Our Reliance on Third Parties
4
Table of Contents
Opus Genetics, Inc.
Form 10-K
Risks Related to Our Intellectual Property
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 ophthalmic biotechnology company developing gene therapies for the treatment of 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:
5
Table of Contents
Opus Genetics, Inc.
Form 10-K
Our expanded pipeline following the Opus Acquisition includes assets from the adeno-associated virus (“AAV”) based gene therapy portfolio of
Private Opus that address mutations in genes that cause different forms of Leber congenital amaurosis (“LCA”), bestrophinopathy, and retinitis pigmentosa.
Our most advanced gene therapy program is designed to address mutations in the LCA5 gene (“LCA5”), which encodes the lebercilin protein. More specifically, we
are developing OPGx-LCA5 to treat LCA5-associated IRD, an early-onset retinal degeneration, and an open-label, dose-escalation Phase 1/2 clinical trial is ongoing. The trial has shown clinical proof-of-concept—one-year data has provided
evidence that the therapy supported visual improvement in three out of three adult patients participating in the trial, each of whom has late-stage disease. Additionally, there were no dose-limiting toxicity or serious adverse events
(“AEs”), with most AEs being mild in nature and resolved within 30 days of treatment at the 1E10 vg/eye dose. There were four observed ocular AEs, including two relating to eye pain, one relating to subretinal hyperreflectivities, and one
relating to corneal abrasion. All were deemed not to be drug-related but instead treatment-related and were managed through the use of steroids and other medications. 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. On March 3, 2025, we held a Type D meeting with the U.S. Food and Drug Administration
(the “FDA”) to discuss the potential regulatory path for OPGx-LCA5, including the design of a potential registrational study. We plan to further interact with the FDA via submission or a formal meeting, with supporting documentation, in
the second quarter of 2025. Enrollment of the first pediatric patient in the LCA5 Phase 1/2 trial occurred in the first quarter of 2025, with the first data anticipated in the third quarter of 2025. The program has received Rare Pediatric
Disease Designation and Orphan Drug Designation from the FDA.
OPGx-BEST1 is another gene therapy candidate in our portfolio, which Private Opus acquired from Iveric Bio, a biopharmaceutical company
focused on the discovery and development of novel treatments for retinal diseases, in late 2022. This asset is being developed for the treatment of IRDs associated with mutations in the BEST1 gene (“Best Disease”), which can lead to
legal blindness. 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. We aim to obtain
preliminary data from a Phase 1/2 study by the first quarter of 2026. The proposed trial design is an open-label, non-randomized, single ascending dose escalation, safety and tolerability study of OPGx-BEST1 in subjects with best
vitelliform macular dystrophy (BVMD) or autosomal recessive BEST1 (ARB), which utilizes a basket approach of three patients per each dose. We are planning to discuss with the FDA an adaptative Phase 1/2/3 trial design, similar to the
design of the OPGx-LCA5 trial, and acceleration to a pivotal study if the majority of patients show a treatment-related fluid resolution on optical coherence tomography (OCT).
Apart from gene therapies, our pipeline also includes Phentolamine Ophthalmic Solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist to reduce pupil size, which is currently
being evaluated in two Phase 3 trials for the treatment of presbyopia and dim (mesopic) light vision disturbances, as well as APX3330, a novel small-molecule inhibitor of Ref-1 designed to slow the progression of non-proliferative diabetic
retinopathy (“NPDR”).
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 develop, manufacture, import, export and commercialize its refractive product candidate Phentolamine Ophthalmic Solution 0.75% (initially known as Nyxol) (“PS”). PS is a once-daily eye drop formulation of
phentolamine mesylate designed to reduce pupil diameter and improve visual acuity. PS was approved by the FDA for the treatment for 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® in September 2023, and the product launched commercially in April 2024. The VEGA-3 Phase 3 clinical trial evaluating PS for the treatment of presbyopia
(age-related blurry near vision) completed enrollment and topline results are expected in the first half of 2025. Additionally, for the treatment of decreased vision under mesopic (low) light conditions following keratorefractive surgery, we
received FDA agreement under Special Protocol Assessment (“SPA”) for LYNX-2, a Phase 3 Trial of PS. LYNX-2 completed enrollment and topline results are expected mid-year 2025. We expect that an additional Phase 3 study of LYNX-3 for the
treatment of decreased vision under mesopic (low) light conditions following keratorefractive surgery will commence in the second half of 2025.
6
Table of Contents
Opus Genetics, Inc.
Form 10-K
APX3330 has completed a Phase 2 clinical study in 103 patients and FDA agreement under SPA was reached for a Phase 3 program. However, due to the capital requirements and developmental
timelines associated with APX3330, we are currently seeking a strategic partner to advance the clinical development of this diabetic retinopathy program and redirecting existing resources toward the acquired gene therapy programs.
Many of the Company’s employees, directors, advisors and consultants have been involved in the development and commercialization of a variety of innovative ophthalmic drugs including approved
products such as LUXTURNA marketed by Spark Therapeutics (a member of the Roche group) and Novartis, IZERVAYTM marketed by Astellas, VABYSMO® marketed by Roche, LUMIFY® marketed by Bausch & Lomb Incorporated, ZIRGAN® marketed by Bausch &
Lomb Incorporated, DUREZOL® marketed by Novartis, RHOPRESSA® marketed by Alcon, ROCKLATAN® marketed by Alcon, VYZULTA® marketed by Bausch & Lomb Incorporated, XIIDRA® marketed by Bausch & Lomb Incorporated, CEQUA® marketed by Sun
Pharmaceuticals Industries Limited, IYUZEHTM marketed by Thea Pharma Inc., DIQUAS® marketed by Santen Company Limited, AzaSite® marketed by Inspire Pharmaceuticals and DEXTENZA® marketed by Ocular Therapeutix, Inc. The management team, led by
Chief Executive Officer George Magrath, MD, collectively has significant experience in operating pharmaceutical companies and discovering, developing, and commercializing treatments in multiple therapeutic areas.
Strategy
The Company’s goal is to develop leading gene therapies to treat IRDs. We will also continue developing or seeking partnerships to develop our product candidates that existed prior to the Opus
Acquisition. The key elements of our strategy we aim to achieve are the following:
OPGx-BEST1 is being developed for the treatment of Best disease, a monogenic central maculopathy which can lead to legal blindness. Preclinical studies conducted
in a naturally occurring genetic canine model of Best disease treated with OPGx-BEST1 provided evidence in support of a first in man clinical trial. We aim to obtain preliminary data from a Phase 1/2 study by the first quarter of 2026.
7
Table of Contents
Opus Genetics, Inc.
Form 10-K
We continue to develop PS in new indications. There are two ongoing Phase 3 studies encompassing the use of PS in two new indications: 1) the VEGA-3 Phase 3 clinical trial evaluating PS for the
treatment of presbyopia (age-related blurry near vision) and 2) the LYNX-2 Phase 3 clinical trial for the treatment of mesopic (low) light conditions following keratorefractive surgery.
The FDA has granted Fast Track designation for Phentolamine Ophthalmic Solution 0.75% as treatment for significant chronic night driving impairment with concomitant increased risk of motor
vehicle accidents and debilitating loss of best spectacle corrected mesopic vision in keratorefractive patients with photic phenomena (i.e., glare, halos, starburst). Fast Track status has been designated to facilitate the development and
expedite the review of drugs to treat serious conditions that fill an unmet medical need.
We expect interim topline data in the first half of 2025 for presbyopia and mid-2025 for decreased vision under mesopic (low) light conditions following keratorefractive surgery. We expect that
an additional Phase 3 study of LYNX-3 for the treatment of decreased vision under mesopic (low) light conditions following keratorefractive surgery will commence in the second half of 2025.
If approved, the use of PS in these indications will also be commercialized by Viatris in the U.S. and major non-U.S. markets pursuant to the Viatris License Agreement.
IRD Pipeline:
8
Table of Contents
Opus Genetics, Inc.
Form 10-K
Phentolamine and APX3330 Pipeline:
Pipeline: OPGx-LCA5, OPGx-BEST1, Other Preclinical IRD Programs, PS, and APX3330
OPGx-LCA5
OPGx-LCA5 is designed to address LCA5, which is a severe, early-onset form of IRD. 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.
In LCA5, the outer segments do not properly develop and photoreceptor function is severely impaired. However, studies have reported evidence that these photoreceptors can survive through the third decade of life, suggesting a broad window of
opportunity for therapeutic intervention through gene augmentation.
LCA5 Mechanism of Disease:
Mechanism of Action
OPGx-LCA5 uses an adeno-associated virus 8 (“AAV8”) vector to deliver a functional LCA5 to the outer retina. OPGx-LCA5 is the same promoter
technology as used with Luxturna. OPGx-LCA5 is administered through a validated surgical delivery method via subretinal injection. OPGx-LCA5’s proposed efficacy endpoints include measurement of functional vision using: 1) the Multi-Luminance
orientation and Mobility Test (MLoMT); 2) Full-Field Stimulus Testing (FST), which measures the retina's sensitivity to light; and 3) microperimetry, which measures point-wise sensitivity to light.
9
Table of Contents
Opus Genetics, Inc.
Form 10-K
LCA5 Disease Overview:
Functional Vision Assessment with a Multi-Luminance orientation and Mobility Test (MLoMT):
10
Table of Contents
Opus Genetics, Inc.
Form 10-K
MLoMT Builds Upon the Success of MLMT®:
Clinical Development Process and Plan
OPGx-LCA5 is currently being evaluated in a Phase 1/2 clinical trial at the University of Pennsylvania designed to evaluate its safety and preliminary efficacy in patients with IRD due to biallelic mutations in
LCA5. New six-month efficacy and safety data on OPGxLCA5 was presented at a virtual KOL event on December 11, 2024 and showed improvement in visual function in the first three adult patients treated, each of whom has late-stage disease.
Treatment of three pediatric subjects (13-17 years of age) was initiated in February, 2025 with all three pediatric patients expected to
receive treatment by the second quarter of 2025. OPGx-LCA5’s proposed efficacy endpoints include measurement of functional vision using: 1) the Multi-Luminance orientation and Mobility Test (MLoMT); 2) Full-Field Stimulus Testing (FST),
which measures the retina's sensitivity to light; and 3) microperimetry, which measures point-wise sensitivity to light.
OPGx-LCA5 Phase 1/2 Study 12-Month Data Summary:
MLoMT: All Treated Subjects Identified More Objects Through 12 Months Compared to Baseline:
11
Table of Contents
Opus Genetics, Inc.
Form 10-K
MLoMT: All Treated Subjects Identified More Objects at Through 12 Compared to Baseline:
Full-field Stimulus Testing: Retinal Sensitivity Gains Comparable to Adult Patients Treated with Luxturna:
12
Table of Contents
Opus Genetics, Inc.
Form 10-K
Broad Clinical Efficacy in Visual Acuity and Pupillometry:
Substantial Improvement in Macular Sensitivity in Subject 01-04:
Uneventful Subretinal Injections and Unchanged Retinal Structure
OPGx-BEST1
OPGx-BEST1 is in development for the treatment of BEST1-associated retinal disease, an IRD that causes vision loss. The BEST1 gene encodes for
bestrophin-1, a protein that functions as a retinal pigment epithelial (“RPE”) cell membrane channel.
Mechanism of Action
The OPGx-BEST1 targets BEST1 using the AAV2 capsid employed in Luxturna and an RPE-specific promoter. This gene therapy approach aims to restore normal function of the RPE cells such that they
can provide proper support to the photoreceptors, the cells that detect light.
13
Table of Contents
Opus Genetics, Inc.
Form 10-K
OPGx-BEST1 Demonstrated Structural and Functional Improvement in an IND-enabling Toxicology Study:
BEST1 Proof of Concept: Restored Retinal Structure Observed in IND-Enabling Studies with OPGx-BEST1:
14
Table of Contents
Opus Genetics, Inc.
Form 10-K
BEST1 Mechanism of Disease:
The BEST1 disease affects ~9000 patients in the U.S alone, and accounts for 3.5% of all IRDs. It is characterized by retinal lesions, with symptoms including dimness of vision, metamorphosphia
(distorted vision), and areas of vision loss or scotoma (blind spot). The BEST1 gene encodes for bestrophin-1, a protein that functions as a RPE cell membrane channel. The BEST1 channel, when activated by calcium (Ca2+) ions, controls chloride
(Cl-) ion transfer into and out of the RPE cell. This function is crucial to the maintenance of homeostasis between the photoreceptors (rods and cones) and RPE cells. Mutations in BEST1 disrupt this homeostasis and result in the breakdown of
the interphotoreceptor matrix (IPM) and microvilli (MV) connections with the RPE. Retinal lesions form containing vitelliform material (“egg-yolk” like) between the RPE and Bruch’s membrane (BM)/choroid (CH). These vitelliform lesions disrupt
and cause atrophy of the RPE. Without support from the RPE, photoreceptor cells critical for normal vision die, resulting in progressive vision loss.
Clinical Development Process and Plan
OPGx-BEST1 which is designed for the treatment of BEST1-associated retinal disease is ready for the clinic. As many of these subjects
are found in Europe, a site will be planned for inclusion as part of the clinical development plan for this asset. This plan is based on the IND-enabling studies, where we observed compelling proof-of-concept efficacy data in a
naturally occurring genetic canine bestrophinopathy model with acceptable safety and tolerability to inform clinical trial implementation. We aim to obtain preliminary data from a Phase 1/2 study by the first quarter of 2026.
15
Table of Contents
Opus Genetics, Inc.
Form 10-K
Other Pre-clinical IRD Programs:
OPGx-RHO
OPGx-RHO is a gene therapy that targets autosomal dominant retinitis pigmentosa caused by RHO mutations (RHO-adRP). RHO-adRP affects
approximately 5,600 people in the U.S., making it one of the most common IRDs, albeit not as common as Best disease.
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 designed to preserve the rod photoreceptors by replacing a patient’s RHO gene with a
functional copy of the gene. We are continuing grant-supported preclinical IND-enabling studies for OPGx-RHO in 2025.
OPGx-RDH12
OPGx-RDH12 is designed to restore protein expression and halt functional deterioration in patients with retinal dystrophy caused by mutations in the retinal dehydrogenase (RDH12) gene.
Patients with RDH12 mutations, which affect approximately 1,100 people in the U.S., 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. 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.
OPGx-MERTK
Mutations in the MERTK gene cause a rod-cone dystrophy with early macular atrophy, with retinitis pigmentosa being the most common phenotype. Preclinical studies have shown proof of concept in
rats and mice and an early clinical trial with an AAV vector was carried out several years ago with mixed results. We are developing OPGx-MERTK as a modern AAV vector for the treatment of MERTK IRD, which affects approximately 600 people in the
U.S.
OPGx-NMNAT1
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 800 people in the U.S. NMNAT1 is an enzyme required for regenerating an essential metabolite, nicotinamide adenine dinucleotide (NAD+), in cell nuclei.
Photoreceptors, in particular, are highly vulnerable to loss of NMNAT1 function. Preclinical data in a mouse model exhibiting key features of the human disease provided evidence of the potential for OPGx-NMNAT1 delivered via AAV to stabilize
disease progression.
16
Table of Contents
Opus Genetics, Inc.
Form 10-K
OPGx-CNGB1
OPGx-CNGB1 is an AAV gene therapy being developed for a late onset form of retinitis pigmentosa due to mutations in the CNGB1 gene, which affects approximately 400 people in the U.S. We are
collaborating with a consortium of university researchers funded by the National Institute of Health (“NIH”) and the Foundation of the NIH’s Bespoke Gene Therapy Consortium to bring this therapy into and through a Phase 1 clinical trial.
RYZUMVI and Phentolamine Ophthalmic Solution 0.75% (PS)
In November 2022, we entered into the Viatris License Agreement with Viatris, pursuant to which we granted Viatris an exclusive license to develop, manufacture, import, export and commercialize
(i) our refractive product candidate PS, for treating (a) reversal of pharmacologically-induced mydriasis, (b) decreased vision under mesopic (low) light conditions after keratorefractive surgery, and (c) presbyopia; and (ii) PS with low dose
pilocarpine for treating presbyopia worldwide except for certain countries and jurisdictions in Asia. PS was approved by the FDA for the treatment of pharmacologically-induced mydriasis under the brand name RYZUMVI in September 2023, which
triggered a $10 million milestone payment under the Viatris License Agreement. RYZUMVI was commercialized by Viatris in April 2024.
PS 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 non-selective alpha-1 and alpha-2 adrenergic antagonist that inhibits activation of the smooth muscle of the iris, reducing pupil diameter (see the below figure).
For the treatment of pharmacologically-induced mydriasis indication, 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.
Pupillary Mechanism:
17
Table of Contents
Opus Genetics, Inc.
Form 10-K
Overview of PS for Presbyopia and Decreased Vision Under Mesopic (Low) Light Conditions after Keratorefractive Surgery:
18
Table of Contents
Opus Genetics, Inc.
Form 10-K
Clinical Development Process and Plan
PS has been assessed in 13 investigator-initiated and company-sponsored Phase 1, Phase 2, and Phase 3 clinical trials. Across all these trials,
over 900 adult subjects have been exposed to at least one dose of phentolamine ophthalmic solution. 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.
VEGA Program: Presbyopia Indication for PS
Phase 3 VEGA-2 Trial (Completed)
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.
Phase 2 VEGA-1 Trial (Completed)
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.
Phase 3 VEGA-3 Trial
We and Viatris are currently conducting the VEGA-3 (NYXP-302) trial as a double-masked, randomized, placebo-controlled, multicenter trial in approximately 545 patients with presbyopia. This
second registration trial will evaluate the efficacy and safety of PS similar to VEGA-2 and include similar primary and key secondary endpoints and analysis, with assessment of tachyphylaxis and an optional extension for a total of 48 weeks.
Topline data is expected in the first half of 2025.
19
Table of Contents
Opus Genetics, Inc.
Form 10-K
VEGA-3 Phase 3 Pivotal Study Design:
LYNX Program: Decreased Vision Under Dim (Mesopic or Low) Light Conditions After Keratorefractive Surgery Indication for PS
PS: Phase 3 LYNX-1 Trial (Completed)
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 percent 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 POS 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 (POS and placebo)
had TEAEs leading to study medication discontinuation.
We are developing PS in partnership with Viatris. In November 2022, we submitted an NDA for PS for the treatment of pharmacologically induced-mydriasis, which was approved in September 2023.
In December 2023, we entered into agreement under SPA with the FDA for PS for decreased vision under dim (mesopic or low) light conditions following keratorefractive surgery.
LYNX-2 Phase 3 Pivotal Study Design:
Based on the positive results observed in the first Phase 3 trial, LYNX-1, we and Viatris are continuing trials for the treatment of decreased vision under dim (mesopic or low) light conditions
following keratorefractive surgery. LYNX-2 has completed enrollment and topline results are expected mid-year 2025. We expect that a clinical trial for LYNX-3 will commence in the second half of 2025.
20
Table of Contents
Opus Genetics, Inc.
Form 10-K
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 signalling 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 (see the below figure for a visual description).
APX3330 Mechanism of Action:
Note: Eylea® is registered trademark of Regeneron and Lucentis® is registered trademark of Roche/Genentech, VABYSMOTM is a registered trademark of the Roche Group, OZURDEX® is registered
trademark of Allergan, XIPERE® is registered trademark of Clearside Biomedical, Inc., ILUVIEN® is registered trademark of Alimera Sciences Inc.
Clinical Development Process and Plan
APX3330 has been studied in over 375 healthy volunteers or patients with hepatitis or cancer or diabetic retinopathy.
In August 2022 we completed ZETA-1, a Phase 2b double-masked, randomized, placebo-controlled, multi-center trial in 103 patients with DR and DME. This study evaluated the effect of 600 mg daily
dose of APX3330 in treating patients with DR, including moderately severe NPDR to mild 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.
21
Table of Contents
Opus Genetics, Inc.
Form 10-K
ZETA-1 Phase 2 Subset Analysis Results:
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.
For APX3330, 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 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 the capital requirements and developmental
timelines of APX3330, which was recently approved for a Phase 3 clinical trial evaluating its oral treatment of moderate to severe NPDR, the Company is seeking a strategic partner to advance the clinical development of this late-stage diabetic
retinopathy program and will redirect its existing resources towards the acquired gene therapy programs.
22
Table of Contents
Opus Genetics, Inc.
Form 10-K
APX3330 is Primed for a Pivotal Study and Available for Partnering:
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 over 300
genetic mutations associated with IRDs. 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. Precedent for one-time gene therapy treatments supports pricing consistent with the value delivered by the product.
Pricing for Approved Gene Therapies:
23
Table of Contents
Opus Genetics, Inc.
Form 10-K
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.
Our pipeline includes PS, which has been approved by the FDA to treat pharmacologically-induced mydriasis and which is currently the subject of the VEGA-3 Phase 3 clinical trial for the
treatment of presbyopia.
Diabetic Retinopathy Market
Diabetic Retinopathy (“DR”) is an eye disease resulting from diabetes, affecting over 10 million patients in the U.S. alone, in which chronically elevated blood sugar levels result in damage to
the microvascular blood vessels of the retina. It is the leading cause of vision loss in adults aged 20-74 years. There are two major types of DR:
Therapies for NPDR and PDR are distinct. For NPDR, treatment is usually directed at observation, lifestyle changes, and control of elevated blood sugars that all lead to the progression of
NPDR. Additionally, the current treatment paradigm is for physicians to wait and monitor early-stage DR/NPDR patients, with anti-VEGF (as defined below), steroid injectable therapy or laser treatment reserved for patients who advance to the
proliferative form of DR or Diabetic Macular Edema (“DME”).
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.
24
Table of Contents
Opus Genetics, Inc.
Form 10-K
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.
We are developing plans for technical transfer and scale-up of the manufacturing process, including analytical support, for pivotal Phase 3
clinical and pre-commercial readiness, at a commercial scale contract drug manufacturing organization (“CDMO”).
OPGx-BEST1
Manufacturing of cGMP-grade OPGx-BEST1 drug substance and drug product for BEST 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 Company does not currently have any active manufacturing agreements. We are developing plans for technical transfer and of the OPGx-BEST1
manufacturing process, including analytical support, for pivotal Phase 3 clinical and pre-commercial readiness.
Other Pre-clinical IRD Assets
The remaining IRD pipeline, including OPGx-RHO, OPGx-RDH12, OPGx-MERTK, OPGx-NMNAT1, and OPGx-GNGB1, 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 Solution (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.
25
Table of Contents
Opus Genetics, Inc.
Form 10-K
License Agreements
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. As of December 31, 2024, there was sufficient uncertainty with regard to any future cash milestone payments under the sublicense agreement that no
liabilities were recorded related to the sublicense agreement.
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. As of December 31, 2024, there was sufficient uncertainly with regard to any
future cash milestone payments under the LCA5/RDH12 Agreement that no liabilities were recorded related to the agreement.
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.
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. As of December 31, 2024, there was sufficient uncertainty with regard to any future cash milestone payments under the Iveric Agreement that no liabilities were recorded related to the agreement.
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. As of December 31, 2024, there was
sufficient uncertainty with regard to any future cash milestone payments under the BEST1 License that no liabilities were recorded related to the agreement.
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.
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. As of December 31, 2024 there was sufficient uncertainty with regard to any future cash milestone payments under the RHO License that no liabilities were recorded related to the agreement.
26
Table of Contents
Opus Genetics, Inc.
Form 10-K
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. As of
December 31, 2024 there was sufficient uncertainty with regard to any future cash milestone payments under the MEEI License that no liabilities were recorded related to the agreement.
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, 2024, 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 patent applications pending in the U.S., Europe, Japan, and additional foreign countries. If the foregoing patent applications are granted, these patents 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 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 2039, not including any patent term extension.
For our MERTK therapeutic program, we own one international patent application to compositions of matter and therapeutic methods using such
compositions of matter. This patent, if granted based on the foregoing patent application to be filed based on the foregoing international patent application, would expire in 2044, not including any patent term extension.
27
Table of Contents
Opus Genetics, Inc.
Form 10-K
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 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 Japan and pending patent applications in the U.S., Europe, and additional foreign countries, whereby the Japanese patent 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 12 U.S. patents, over seven pending U.S. non-provisional patent applications, a 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 one U.S. patent 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 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, pending U.S. patent application, and pending European 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.
APX3330
As of December 31, 2024, the patent estate that we in-license for APX3330 and related compounds contains nine U.S. patents and two pending U.S. non-provisional patent applications, as well as
issued patents in Europe, Japan, and additional foreign countries, and pending patent applications in Europe, Japan, and additional foreign countries. 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.
28
Table of Contents
Opus Genetics, Inc.
Form 10-K
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, one pending U.S. patent application, 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 2039, not including any
patent term extension.
In addition, as of December 31, 2024, we own one U.S. provisional patent application, one 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 one pending international patent application with counterpart patent applications pending in the U.S., Taiwan, and Argentina 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.
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 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 RDH12 gene, there is an
investigator-initiated trial in China and a program from MeiraGTX. For the Rho program, Octant Bio appears to have a preclinical program. Cell therapies and optogenetics are potential competition for late stages for our diseases from genes of
interest at which point, gene augmentation may be less efficacious.
PS
Phentolamine Ophthalmic Solution 0.75% is in development for additional indications of presbyopia as well as decreased visual acuity under low light conditions following keratorefractive
surgery. There are multiple potential competitors for the treatment of presbyopia including Lenz Therapeutics (LNZ100 - 1.75% Aceclidine) and AbbVie (VUITY® (pilocarpine hydrochloride ophthalmic solution) - 1.25%). We are not aware of direct
competition for the treatment of DLD following keratorefractive surgery.
In January 2025, we received a Paragraph IV Certification Notice (“Notice Letter”) that Sandoz, Inc., a provider of generic and biosimilar medicines (“Sandoz”), submitted an Abbreviated New
Drug Application (ANDA) to the FDA seeking approval to manufacture, use or sell a generic version of RYZUMVI for the reversal of pharmacologically-induced mydriasis in the U.S. prior to the expiration of six of our patents listed in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations publication (the “Orange Book”). The Notice Letter alleges that these patents are invalid or unenforceable or will not be infringed by the
generic product described in Sandoz’s ANDA. If the challenge by Sandoz is successful, it could result in the introduction of a generic competitor to the market before the expiration of our patents, thereby reducing our market share and
potential future revenue from sales of RYZUMVI for reversal of pharmacologically-induced mydriasis. In March 2025, in collaboration with our commercialization partner for RYZYMVI®, we filed a complaint for patent infringement of certain
RYZYMVI® patents against Sandoz in the District of New Jersey in response to Sandoz’s ANDA filing. The complaint seeks, among other relief, equitable relief enjoining Sandoz from infringing the RYZUMVI patents.
29
Table of Contents
Opus Genetics, Inc.
Form 10-K