Ocuphire Pharma, Inc. [OCUP] Filings

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PART I			7
	ITEM 1.	BUSINESS	7
	ITEM 1A.	RISK FACTORS	44
	ITEM 1B.	UNRESOLVED STAFF COMMENTS	83
	ITEM 1C.	CYBERSECURITY	83
	ITEM 2.	PROPERTIES	84
	ITEM 3.	LEGAL PROCEEDINGS	84
	ITEM 4.	MINE SAFETY DISCLOSURES	84
PART II
	ITEM 5.	MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES	85
	ITEM 6.	[RESERVED]	85
	ITEM 7.	MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS	85
	ITEM 7A.	QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK	99
	ITEM 8.	FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA	100
	ITEM 9.	CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE	100
	ITEM 9A.	CONTROLS AND PROCEDURES	100
	ITEM 9B.	OTHER INFORMATION	101
	ITEM 9C.	DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS	101
PART III
	ITEM 10.	DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE	102
	ITEM 11.	EXECUTIVE COMPENSATION	102
	ITEM 12.	SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS	102
	ITEM 13.	CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE	102
	ITEM 14.	PRINCIPAL ACCOUNTANT FEES AND SERVICES	102
PART IV
	ITEM 15.	EXHIBITS AND FINANCIAL STATEMENT SCHEDULES	103
	ITEM 16.	FORM 10-K SUMMARY	108
SIGNATURES

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We depend heavily on the success of our product pipeline and we (or our current or future strategic partners). Ocuphire and/or Viatris may never complete clinical development of, receive marketing approval for, or successfully commercialize, PS alone or as adjunctive therapy with low dose pilocarpine (LDP), APX3330, or any of our other product candidates. Moreover, if we (or our strategic partner) fail to adequately develop and commercialize APX3330 or PS, our business may be materially harmed.

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The results of previous clinical trials may not be predictive of future results, and the results of our current and planned clinical trials may not satisfy the requirements of the FDA or non-U.S. regulatory authorities.

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If we experience delays or difficulties in the enrollment of patients in clinical trials, our ability to conduct and complete clinical trials, and our ability to seek and receive necessary regulatory approvals, could be delayed or prevented.

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Changes in regulatory requirements or FDA guidance, or unanticipated events during our clinical trials, may result in changes to clinical trial protocols or additional clinical trial requirements, which could result in increased costs to us or delays in its development timeline.

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We or others could discover that our product candidates lack sufficient efficacy, or sufficient efficacy compared to competitor products or that they cause undesirable side effects that were not previously identified, which could delay or prevent regulatory approval or commercialization.

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Even if we receive marketing approval for our product candidates in the United States, we may never receive regulatory approval to market such product candidates outside of the United States.

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We face substantial competition and rapid technological change, which may result in others discovering, developing, or commercializing products before or more successfully than we do.

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We do not currently have any sales or marketing infrastructure in place and, if APX3330 is approved, we may face difficulties in establishing sales and marketing capabilities or engaging third parties to sell, market and distribute APX3330.

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Our future commercial success depends upon attaining significant market acceptance of our product candidates, if approved, among physicians, patients, third-party payors, and others in the medical community.

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If the FDA or a comparable foreign regulatory authority approves generic versions of our product candidates that receive marketing approval, or if such authorities do not grant our product candidates appropriate periods of exclusivity before approving generic versions of our products, the sales of our products could be adversely affected.

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We have not generated any revenue from sales of any products, and we expect to incur losses for the foreseeable future and may never achieve or maintain profitability.

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Our relatively short operating history may make it difficult for investors to evaluate our business to date and to assess our future viability.

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We will need substantial additional capital in the future. If additional capital is not available or is not available on acceptable terms (whether as a result of financial services industry changes, our financial performance or otherwise), we will have to delay, reduce or cease operations.

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Raising additional capital may cause dilution to our stockholders, restrict our operations, or require us to relinquish rights to our technologies or product candidates.

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Worldwide economic and social instability or adverse global economic conditions could adversely affect our revenue, financial condition, or results of operations.

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Our employees or our representatives may engage in misconduct or other improper activities, including violating applicable regulatory standards and requirements, which could significantly harm our business.

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Product liability lawsuits against us, or our suppliers and manufacturers, could cause us to incur substantial liabilities and could limit commercialization of any product candidate that we may develop.

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Federal legislation and actions by state and local governments could permit reimportation of drugs from foreign countries into the United States, which could adversely affect our operating results when the drugs are sold at lower prices in foreign countries.

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We rely on third parties to conduct our preclinical and clinical trials and perform other tasks for us. If these third parties do not successfully carry out their contractual duties, meet expected deadlines or comply with regulatory requirements, we may not be able to obtain regulatory approval for or commercialize our product candidates and our business could be harmed.

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We rely completely on third parties to supply and manufacture bulk drug substances and to formulate and package nonclinical and clinical drug supplies of our product candidates as well as to conduct analytical testing of drug substances and products in the manufacturing processes and we intend to rely on third parties to produce and test commercial supplies of our current and any future product candidates.

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We have entered and may enter into licensing arrangements for the development or sale of product candidates (such as the Viatris License Agreement (as defined below)) and may form or seek additional strategic alliances or enter into licensing arrangements in the future, including for APX3330. If we are unsuccessful in forming or maintaining these alliances on favorable terms, our business could be harmed and we may have to alter development, manufacturing and commercialization plans.

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If we engage in acquisitions, in-licensing or strategic partnerships, this may increase our capital requirements, dilute our stockholders, cause us to incur debt or assume contingent liabilities and subject us to other risks.

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If we are unable to obtain and maintain sufficient patent protection for our product candidates, our competitors could develop and commercialize products or technology similar or identical to those of us, which would adversely affect our ability to successfully commercialize any product candidates we may develop, our business, results of operations, financial condition and prospects.

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If we do not obtain protection under the Hatch-Waxman Act and similar foreign legislation by extending the patent terms and obtaining data exclusivity for our product candidate, our business may be materially harmed.

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We may not be able to protect or practice our intellectual property rights throughout the world.

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Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment, and other requirements imposed by governmental agencies, and our patent protection could be reduced or eliminated for noncompliance with these requirements.

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We are dependent on our key personnel, and if we are not successful in attracting and retaining highly qualified personnel, we may not be able to successfully implement our business strategy.

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A variety of risks associated with operating internationally for us and our collaborators could adversely affect our business.

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Our business and operations would suffer in the event of system failures or unplanned events, including cyber incidents, network security breaches, service interruptions, or data corruption.

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We currently have a substantial number of shares subject to potential issuance associated with our Equity Line of Credit arrangement. The issuance or sale of shares under our ELOC arrangement would substantially increase the number of shares outstanding and result in dilution to our security holders. This might substantially decrease the market price of the common stock.

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We do not anticipate paying any cash dividends in the foreseeable future.

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If we fail to comply with the continued listing standards of the Nasdaq Capital Market, our common stock could be delisted. If it is delisted, our common stock and the liquidity of our common stock would be impacted.

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The market price of our common stock may fluctuate significantly.

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We may be subject to securities litigation, which is expensive and could divert management attention.

ITEM 1.

BUSINESS

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Advance the clinical development of our products.

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Maintain and expand its intellectual property portfolio. Ocuphire owns an exclusive worldwide sublicense for the Ref-1 Inhibitor program, including its product candidate APX3330, for all its ophthalmic and diabetic indications, and compositions and methods of use for Ref-1 pipeline candidates, including APX2009 and APX2014.

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Maximize the value of APX3330 and PS. Ocuphire may seek one or more partners to develop and commercialize APX3330 both in and/or outside of the United States.

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Evaluate in-licensing and acquisition opportunities. Ocuphire’s team is well qualified to identify and in-license or acquire clinical-stage assets and continually evaluates opportunities to expand and diversify its pipeline.

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Potential to be the first oral therapy. Compared to frequent intravitreal anti-VEGF injections, associated with ocular complications, twice a day oral administration of APX3330 could be a convenient, new preventative therapeutic option or adjunctive treatment option for large number of patients with retinal diseases, if approved.

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Upstream target implicated in two validated pathways. APX3330 is designed to modulate two validated cell signaling pathways (angiogenesis and inflammation) known to cause various retinal diseases. Moreover, the APX3330 mechanism of action is distinct in working upstream of the current anti-VEGF therapies, suggesting that it could complement anti-VEGF therapies and potentially reduce frequency of doctor visits and intravitreal injections.

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Favorable tolerability profile. In 12 completed Phase 1 and Phase 2 clinical trials, APX3330 was observed to be well-tolerated. The adverse events (“AEs”) were mostly infrequent and mild with transient pruritis being the most common.

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Potential benefit of systemic administration.  As a systemic agent, APX3330 can be expected to treat bilateral binocular (both eyes) retinal vascular disease.

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Oral tablet with scalable manufacturing process. APX3330 is formulated as an oral tablet with favorable stability characteristics, and its active pharmaceutical ingredient is a small molecule with the advantages of standardized, scalable, and lower-cost manufacturing processes.

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DR, the leading cause of vision loss in adults aged 20–74 years, which results from chronic elevations of glucose in the blood that leads to cell damage in the retina. Retinal key opinion leaders’ feedback suggests that slowing of DR progression with an oral agent would be a useful treatment in patients with background DR and good visual function.

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DME, one of the most common complications of DR, in which vascular leakage causes swelling of the retinal macula and a loss of visual acuity.

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wAMD, a chronic eye disorder that causes visual distortions in the central part of one’s vision, in which abnormal blood vessels leak fluid or blood into the macula, the part of the eye that is critical for central and color vision.

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GA, an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible vision loss.

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Presbyopia, a condition in which the eye’s lens loses elasticity, affecting its ability to focus on near objects. Presbyopia typically occurs after age 40 and most patients use reading glasses in order to read or see objects close to them. VuityTM approved in October 2021, and QLOSI™ approved in October 2023 are the only two approved eye drops for the treatment of presbyopia.

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Decreased vision under dim (mesopic or low) light conditions after keratorefractive surgery, a condition in which peripheral imperfections (aberrations) of the cornea scatter light when the pupil opens wide in dim light. Patients experience glare, halos, starbursts, and decreased contrast sensitivity. decreased visual acuity under dim (mesopic) light conditions is a new indication with no approved therapies.

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Non-proliferative DR, or NPDR. NPDR is an earlier stage of DR and can progress into more severe forms of DR over time if untreated and if exposure to elevated blood sugar levels persists.

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Proliferative DR, or PDR. PDR is a more advanced stage of DR than NPDR. It is characterized by retinal neovascularization and, if left untreated, leads to permanent damage and blindness.

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completion of preclinical laboratory tests, animal studies and formulation studies in compliance, as applicable, with the Animal Welfare Act and FDA’s good laboratory practice, or GLP, regulations;

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submission to the FDA of an IND, which must take effect before human clinical trials may begin;

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approval by an independent institutional review board, or IRB, representing each clinical site before each clinical trial may be initiated;

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performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, and other applicable regulations to establish the safety and efficacy of the proposed drug product for each proposed indication;

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manufacturing, packaging, labelling, and distribution of drug substances and drug products consistent with the FDA’s Good Manufacturing Practice (GMP) regulations which are utilized in the GLP non-clinical and GCP clinical studies to investigate the drug candidate;

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development of product label, package inserts, and prescriber information that is intended to be used and included with the commercial product;

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preparation and submission to the FDA of an NDA;

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review of the product by an FDA advisory committee, where appropriate or if applicable;

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satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which the product, or components thereof, are produced to assess compliance with current Good Manufacturing Practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to preserve the product’s identity, strength, quality and purity;

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satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity of the clinical data;

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payment of user fees, if appropriate, and securing FDA approval of the NDA; and

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compliance with any post-approval requirements, including Risk Evaluation and Mitigation Strategies, or REMS, and post-approval studies required by the FDA.

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Phase 1. The drug is initially introduced into healthy human subjects or, in certain indications such as cancer, patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism, distribution, excretion and, if possible, to gain an early indication of its effectiveness and to determine optimal dosage.

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Phase 2. The drug is administered to a limited patient population to identify possible adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to determine dosage tolerance and optimal dosage.

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Phase 3. The drug is administered to an expanded patient population, generally at geographically dispersed clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product and to provide adequate information for the labeling of the product.

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restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

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fines, warning letters or holds on post-approval clinical trials;

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refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or revocation of product license approvals;

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product seizure or detention, or refusal to permit the import or export of products; or

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injunctions or the imposition of civil or criminal penalties.

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A special, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs, although this fee would not apply to sales of certain products approved exclusively for orphan indications;

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Expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;

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Expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program (“MDRP”) by increasing the minimum rebate for both branded and generic drugs and revising the definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices and extending rebate liability to prescriptions for individuals enrolled in Medicare Advantage plans; addressed a new methodology by which rebates owed by manufacturers under the MDRP are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

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Expanded the types of entities eligible for the 340B drug discount program;

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A new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and

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Established the Center for Medicare and Medicaid Innovation within the Centers of Medicare and Medicaid Services (“CMS”) to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

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The federal Anti-Kickback Statute, which is a criminal law that prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to have committed a violation. Violations of the federal Anti-Kickback Statute can result in significant civil monetary penalties and criminal fines, as well as imprisonment and exclusion from participation in government health care programs;

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The federal civil False Claims Act, which may be enforced through civil whistleblower or qui tam actions and imposes significant civil penalties, treble damages and potential exclusion from government health care programs against individuals or entities for, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or for making a false record or statement material to an obligation to pay the federal government or for knowingly and improperly avoiding, decreasing or concealing an obligation to pay money to the federal government. Further, a violation of the federal Anti-Kickback Statute can serve as a basis for liability under the federal civil False Claims Act. There is also the federal Criminal False Claims Act, which is similar to the federal Civil False Claims Act and imposes criminal liability on those that make or present a false, fictitious or fraudulent claim to the federal government;

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The federal Civil Monetary Penalties Law, which authorizes the imposition of substantial civil monetary penalties against an entity that engages in activities including, among others (1) knowingly presenting, or causing to be presented, a claim for services not provided as claimed or that is otherwise false or fraudulent in any way; (2) arranging for or contracting with an individual or entity that is excluded from participation in federal health care programs to provide items or services reimbursable by a federal health care program; (3) violations of the federal Anti-Kickback Statute; or (4) failing to report and return a known overpayment;

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The federal payment transparency tracking and reporting requirements known as the federal Physician Payments Sunshine Act, implemented as the Open Payments Program, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, among others, to track and report annually to CMS, within the United States Department of Health and Human Services (“HHS”), information related to payments and other transfers of value made by that entity to US-licensed physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered nurse anesthetists, certified nurse midwives, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members. Failure to timely, accurately, and completely submit the required information for all payments, transfers of value and ownership or investment interests may result in civil monetary penalties;

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The federal Health Insurance Portability and Accountability Act of 1996 (“HIPAA”) which imposes criminal and civil liability for, among other things, executing or attempting to execute a scheme to defraud any healthcare benefit program, including any third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statements or representations, or making false statements relating to healthcare benefits, items or services. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation

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HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act of 2009, which mandates, among other things, the adoption of uniform standards for the electronic exchange of information in common health care transactions as well as standards relating to the privacy and security of individually identifiable health information. These standards require the adoption of administrative, physical and technical safeguards to protect such information. In addition, many states have enacted comparable laws addressing the privacy and security of health information, some of which are more stringent than HIPAA. Failure to comply with these laws can result in the imposition of significant civil and criminal penalties;

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State laws that require the reporting of certain pricing information, including information pertaining to and justifying price increases, prohibit prescription drug price gouging; or impose payment caps on certain pharmaceutical products deemed by the state to be “high cost”; and

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Analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures.

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Additionally, we expect our products, if and when approved, may be eligible for coverage under Medicare, the federal health care program that provides health care benefits to the aged and disabled. Specifically, we expect our products would be primarily reimbursed under Medicare Part D, which provides an outpatient prescription drug benefit for Medicare beneficiaries. Medicare Part D is implemented through private insurance plans under contractual arrangements between the plans and the federal government. Similar to pharmaceutical coverage through private health insurance, Part D plans develop formularies, impose utilization controls (such as prior authorization, step therapy, and quantity limits), and negotiate discounts from drug manufacturers. Because of this, the list of prescription drugs covered by Part D plans varies by plan. However, with limited exceptions, individual plans are required by statute to cover certain therapeutic categories and classes of drugs or biologics and to have at least two drugs in each unique therapeutic category or class. Our products may also be covered and reimbursed under other government programs, including those discussed below:

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The MDRP requires pharmaceutical manufacturers to enter into and have in effect a national rebate agreement with the Secretary of the Department of Health and Human Services as a condition for states to receive federal matching funds for the manufacturer’s outpatient drugs furnished to Medicaid patients. Under the MDRP, manufacturers must pay a rebate to each state Medicaid program for quantities of products utilized on an outpatient basis (with some exceptions) that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program. MDRP rebates are calculated using a statutory formula, state-reported utilization data, and pricing data that are calculated and reported by manufacturers on a monthly and quarterly basis to CMS. These data include the AMP and, in the case of single source and innovator multiple source products, the best price for each drug.

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The 340B drug pricing program requires participating manufacturers to agree to charge statutorily-defined covered entities no more than the 340B “ceiling price” for the manufacturer’s covered outpatient drugs. These 340B covered entities include health care organizations that have certain federal designations or receive funding from specific federal programs, including Federally Qualified Health Centers, Ryan White HIV/AIDS Program grantees, and certain types of hospitals and specialized clinics, as well as certain hospitals that serve a disproportionate share of low-income patients. The ACA expanded the 340B program to also include certain children’s hospitals, certain free-standing cancer hospitals, critical access hospitals, certain rural referral centers and certain sole community hospitals, each as defined by ACA. The 340B ceiling price is calculated using a statutory formula, which is based on the AMP and rebate amount for the covered outpatient drug as calculated under the MDRP, and in general, products subject to the MDRP are also subject to the 340B ceiling price calculation and discount requirement. Any changes to the definition of Medicaid AMP and the Medicaid rebate amount also could affect our 340B ceiling price calculation for our products and could negatively impact our results of operations.

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Federal law further requires that for a company to be eligible to have its products paid for with federal funds under the MDRP and Medicare Part B programs, as well as to be purchased by certain federal agencies and grantees, it also must participate in the Department of Veterans Affairs (“VA”) Federal Supply Schedule (“FSS”) pricing program. To participate, manufacturers are required to enter into an FSS contract and other agreements with the VA for any covered drugs. Under these agreements, manufacturers must make such products available to the “Big Four” federal agencies—the VA, the Department of Defense (“DoD”), the Public Health Service (including the Indian Health Service), and the Coast Guard—at pricing that is capped pursuant to a statutory federal ceiling price (“FCP”), formula set forth in Section 603 of the Veterans Health Care Act of 1992 (“VHCA”). The FCP is based on a weighted average non-federal average manufacturer price (“Non-FAMP”), which manufacturers are required to report on a quarterly and annual basis to the VA.

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Any failure to comply with price reporting and rebate payment obligations under federal healthcare programs could negatively impact our financial results. Civil monetary penalties can be applied if we are found to have knowingly submitted any false price information to the government, if we are found to have made a misrepresentation in the reporting of our average sales price, or if we fail to submit the required price data on a timely basis. Such conduct also could provide a basis for other potential liability under other federal laws such as the False Claims Act.

ITEM 1A.

RISK FACTORS

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delays in the launch or difficulties in the widespread commercialization of RYZUMVI (currently the launch is anticipated in the first half of 2024);

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delays in, termination, or numerous unforeseen events during, or as a result of, manufacturing or clinical trials;

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obtaining unfavorable results from nonclinical and clinical studies for our product candidates;

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the cost of clinical trials being greater than anticipated;

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the willingness of patients or medical investigators to follow our clinical trial protocols and the number of patients willing to participate;

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delays in applying for and receiving marketing and NDA approvals from applicable regulatory authorities for our product candidates;

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other government or regulatory delays and changes in regulatory requirements, policy and guidelines may require us to perform additional clinical trials or use substantial additional resources to obtain regulatory approval;

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issues with making arrangements with third-party manufacturers for commercial quantities of RYZUMVI and our product candidates and receiving regulatory approval of our manufacturing processes and our third-party manufacturers’ facilities from applicable regulatory authorities;

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establishing sales, marketing, and distribution capabilities and launching commercial sales of RYZUMVI  and our product candidates, if and when approved, whether alone or in collaboration with others;

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acceptance of RYZUMVI and our product candidates by patients, the medical community, and third-party payors;

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effectively competing with other therapies, including the existing standard-of-care;

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maintaining a continued acceptable safety profile of RYZUMVI and our product candidates following approval;

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obtaining and maintaining coverage and adequate reimbursement from third-party payors;

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obtaining and maintaining patent and trade secret protection and regulatory exclusivity;

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protecting our rights in our intellectual property portfolio related to RYZUMVI and our product candidates; and

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our ability to fulfill requests for additional data regarding our product candidates.

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In addition, under the Apexian License Agreement, Ocuphire has rights to certain compounds for use in ophthalmic and diabetic diseases. Ocuphire does not control the development of these compounds in other non-ophthalmic indications.

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Viatris may not be able to manufacture our products in a timely or cost-effective manner;

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Viatris may not timely perform its obligations under the Viatris License Agreement;

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Viatris may fail to effectively commercialize our products;

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Viatris may not be able to sublicense RYZUMVI or PS to one or more suitable parties outside the United States; or

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Contractual disputes or other disagreements between us and Viatris, including those regarding the development, manufacture, sub licensure and commercialization of our products, interpretation of the License Agreement, and ownership of proprietary rights. Viatris may select a new development partner for RYZUMVI and PS in the U.S. upon 90 days’ notice to Ocuphire.

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severity of the disease under investigation;

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availability and efficacy of medications already approved for the disease under investigation;

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eligibility criteria and visit schedule for the trial in question;

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competition for eligible patients with other companies conducting clinical trials for product candidates seeking to treat the same indication or patient population;

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our payments for conducting clinical trials;

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perceived risks and benefits of the product candidate under study;

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efforts to facilitate timely enrollment in clinical trials;

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patient referral practices of physicians;

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the ability to monitor patients adequately during and after treatment;

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proximity and availability of clinical trial sites for prospective patients; and

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the ability of patients to participate in clinical trials during any public health emergencies.

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discover that they are less effective, or identify undesirable side effects caused by our product candidates:

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regulatory authorities may withdraw their approval of the product;

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we may be required to recall the product, change the way this product is administered, conduct additional clinical trials, or change the labeling or distribution of the product (including REMS);

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additional restrictions may be imposed on the marketing of, or the manufacturing processes for, the product;

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we may be subject to fines, injunctions, or the imposition of civil or criminal penalties;

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we could be sued and held liable for harm caused to patients;

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the product may be rendered less competitive and sales may decrease; or

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our reputation may suffer generally among both clinicians and patients.

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the successful launch and widespread commercialization of RYZUMVI;

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obtain favorable results from and complete the nonclinical and clinical development of our product candidates for their planned indications, including successful completion of additional clinical trials for these indications;

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submit applications to regulatory authorities for both product candidates and receive timely marketing approvals in the United States and foreign countries;

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establish and maintain commercially viable supply and manufacturing relationships with third parties that can provide adequate, in both amount and quality, products and services to support clinical development and meet the market demand for RYZUMVI and our product candidates that we develop, if approved;

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establish sales and marketing capabilities to effectively market and sell our product candidates in the United States or other markets, either alone or with a pharmaceutical partner;

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address any competing products and technological and market developments;

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obtain coverage and adequate reimbursement for customers and patients from government and third-party payors for RYZUMVI and our product candidates that we develop; and

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achieve market acceptance of RYZUMVI and our product candidates.

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Delayed access to deposits or other financial assets or the uninsured loss of deposits or other financial assets;

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Loss of access to revolving existing credit facilities or other working capital sources and/or the inability to refund, roll over or extend the maturity of, or enter into new credit facilities or other working capital resources;

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Potential or actual breach of contractual obligations that require us to maintain letters or credit or other credit support arrangements; or

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Termination of cash management arrangements and/or delays in accessing or actual loss of funds subject to cash management arrangements.

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the scope, size, rate of progress, results, and costs of researching and developing our product candidates, and initiating and completing our nonclinical studies and clinical trials;

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the cost, timing and outcome of our efforts to obtain further marketing approval for our product candidates in the United States and other countries, including to fund the preparation and filing of NDAs with the FDA for our product candidates and to satisfy related FDA requirements and regulatory requirements in other countries;

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the number and characteristics of any additional product candidates we develop or acquire, if any;

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our ability to establish and maintain collaborations on favorable terms, if at all;

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the amount of revenue, if any, from commercial sales, should our product candidates receive marketing approval;

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the costs associated with commercializing our product candidates, if we receive marketing approval, including the cost and timing of developing sales and marketing capabilities or entering into strategic collaborations to market and sell our product candidates;

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the cost of manufacturing our product candidates or products we successfully commercialize; and

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the costs associated with general corporate activities, such as the cost of filing, prosecuting and enforcing patent claims and making regulatory filings.

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litigation involving patients taking our drugs;

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restrictions on such drugs, manufacturers, or manufacturing processes;

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restrictions on the labeling or marketing of a drug;

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restrictions on drug distribution or use;

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requirements to conduct post-marketing studies or clinical trials;

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warning letters or untitled letters;

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withdrawal of the drugs from the market;

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refusal to approve pending applications or supplements to approved applications that we submit;

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product recall or public notification or medical product safety alerts to healthcare professionals;

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fines, restitution, or disgorgement of profits or revenues;

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suspension or withdrawal of marketing approvals;

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damage to relationships with any potential collaborators;

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unfavorable press coverage and damage to our reputation;

•

refusal to permit the import or export of drugs;

•

product seizure; or

•

injunctions or the imposition of civil or criminal penalties.

•

comply with the regulations of the FDA and applicable non-U.S. regulators;

•

provide accurate information to the FDA and applicable non-U.S. regulators;

•

comply with healthcare fraud and abuse laws and regulations in the United States and abroad;

•

report financial information or data accurately; or

•

disclose unauthorized activities to us.

•

the inability to recruit and retain adequate numbers of effective sales and marketing personnel or enter into distribution agreements with third parties;

•

the inability of sales personnel to obtain access to physicians or educate an adequate number of physicians as to the benefits of our products;

•

the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines;

•

unforeseen costs and expenses associated with creating an independent sales and marketing organization; and

•

the inability to obtain sufficient coverage and reimbursement from third-party payors and governmental agencies.

•

If we enter into arrangements with third parties to perform sales, marketing, and distribution services, our product revenues or the profitability of these product revenues to us are likely to be lower than if we were to market and sell a product that we developed ourselves. In addition, we may not be successful in entering into arrangements with third parties to sell and market any product candidate or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market a drug effectively. If we do not establish sales and marketing capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.

•

efficacy and potential advantages compared to alternative treatments;

•

the ability to offer our product for sale at competitive prices;

•

the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

•

any restrictions on the use of our product together with other medications;

•

interactions of our product with other medicines patients are taking;

•

inability of certain types of patients to take our product;

•

demonstrated ability to treat patients and, if required by any applicable regulatory authority in connection with the approval for target indications as compared with other available therapies;

•

the relative convenience and ease of administration as compared with other treatments available for approved indications;

•

the prevalence and severity of any adverse side effects;

•

limitations or warnings contained in the labeling approved by the FDA;

•

availability of alternative treatments already approved or expected to be commercially launched in the near future;

•

the effectiveness of our sales and marketing strategies;

•

our ability to increase awareness through marketing efforts;

•

guidelines and recommendations of organizations involved in research, treatment and prevention of various diseases that may advocate for alternative therapies;

•

our ability to obtain sufficient third-party coverage and adequate reimbursement;

•

the willingness of patients to pay out-of-pocket in the absence of third-party coverage; and

•

physicians or patients may be reluctant to switch from existing therapies even if potentially more effective, safe or convenient.

•

decreased demand for any product candidate that we are developing;

•

injury to our reputation and significant negative media attention;

•

withdrawal of clinical trial participants;

•

increased FDA warnings on product labels;

•

significant costs to defend the related litigation;

•

substantial monetary awards to trial participants or patients;

•

distraction of management’s attention from our primary business;

•

loss of revenue;

•

the inability to commercialize any product candidate that we may develop;

•

the initiation of investigations by regulators; and

•

the inability to take advantage of limitations on product liability lawsuits that apply to generic drug products, which could increase our exposure to liability for products deemed to be dangerous or defective.

•

fail to comply with contractual obligations;

•

experience regulatory compliance issues;

•

undergo changes in ownership or management;

•

undergo changes in priorities or become financially distressed; or

•

form relationships with other entities, some of which may be our competitors.

•

collaborators have significant discretion in determining the efforts and resources that they will apply to these collaborations;

•

collaborators may not perform their obligations as expected;

•

collaborators may not pursue development and commercialization or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding, or external factors such as an acquisition that diverts resources or creates competing priorities;

•

collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate for clinical testing;

•

collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidate if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more attractive than ours;

•

a collaborator with marketing and distribution rights to one or more product candidates may not commit sufficient resources to the marketing or distribution of any such product candidate;

•

collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our proprietary information or expose us to litigation;

•

collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation and potential liability;

•

disputes may arise between us and collaborators that result in the delay or termination of research, development, or commercialization of our product candidates, or in litigation or arbitration that diverts management attention and resources;

•

we may lose certain valuable rights under circumstances identified in our collaborations, including if we undergo a change of control;

•

collaborations may be terminated and such terminations may create a need for additional capital to pursue further development or commercialization of the applicable product candidates;

•

collaborators may learn about our discoveries and use this knowledge to compete with us in the future;

•

the results of collaborators’ nonclinical or clinical studies could harm or impair other development programs;

•

there may be conflicts between different collaborators that could negatively affect those collaborations and potentially others;

•

the number and nature of our collaborations could adversely affect our attractiveness to potential future collaborators or acquirers;

•

collaboration agreements may not lead to development or commercialization of our product candidate in the most efficient manner or at all. If a present or future collaborator of us were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program under such collaboration could be delayed, diminished, or terminated; and

•

collaborators may be unable to obtain the necessary marketing approvals.

•

increased operating expenses and cash requirements;

•

the assumption of indebtedness or contingent liabilities;

•

the issuance of our equity securities which would result in dilution to our stockholders;

•

assimilation of operations, intellectual property, products and product candidates of an acquired company, including difficulties associated with integrating new personnel;

•

the diversion of management’s attention from our existing product candidates and initiatives in pursuing such an acquisition or strategic partnership;

•

retention of key employees, the loss of key personnel, and uncertainties in our ability to maintain key business relationships;

•

risks and uncertainties associated with the other party to such a transaction, including the prospects of that party and their existing products or product candidates and regulatory approvals; and

•

our inability to generate revenue from acquired intellectual property, technology and/or products sufficient to meet our objectives or even to offset the associated transaction and maintenance costs.

•

any of our patents, or any of our pending patent applications, if issued, will include claims having a scope sufficient to protect our product candidates;

•

any of our pending patent applications will result in issued patents;

•

we will be able to successfully commercialize our product candidates, if approved, before our relevant patents expire;

•

we were the first to make the inventions covered by each of our patents and pending patent applications;

•

we were the first to file patent applications for these inventions;

•

others will not develop similar or alternative technologies that do not infringe our patents;

•

any of our patents will be valid and enforceable;

•

any patents issued to us will provide a basis for an exclusive market for our commercially viable products, will provide us with any competitive advantages or will not be challenged by third parties;

•

we will develop additional proprietary technologies or product candidates that are separately patentable; or

•

our commercial activities or products will not infringe upon the patents of others.

•

the scope of rights granted under the license agreement and other interpretation-related issues;

•

the extent to which our product candidates, technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

•

the sublicensing of patent and other rights under our collaborative development relationships;

•

our diligence obligations under the license agreement and what activities satisfy those diligence obligations;

•

the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property; and

•

the priority of invention of patented technology.

•

compliance with differing or unexpected regulatory requirements for our product candidates;

•

different medical practices and customs affecting acceptance of our product candidates, if approved, or any other approved product in the marketplace;

•

language barriers;

•

the interpretation of contractual provisions governed by foreign law in the event of a contract dispute;

•

difficulties in staffing and managing foreign operations, and an inability to control commercial or other activities where it is relying on third parties;

•

workforce uncertainty in countries where labor unrest is more common than in the United States;

•

potential liability under the Foreign Corrupt Practice Act of 1977 or comparable foreign regulations;

•

production shortages resulting from any events affecting raw material supply or manufacturing capability abroad;

•

foreign government taxes, regulations, and permit requirements;

•

U.S. and foreign government tariffs, trade restrictions, price and exchange controls, and other regulatory requirements;

•

economic weakness, including inflation, natural disasters, war, events of terrorism, or political instability in particular foreign countries;

•

fluctuations in currency exchange rates, which could result in increased operating expenses and reduced revenues;

•

compliance with tax, employment, immigration, and labor laws, regulations, and restrictions for employees living or traveling abroad;

•

changes in diplomatic and trade relationships; and

•

challenges in enforcing our contractual and intellectual property rights, especially in those foreign countries that do not respect and protect intellectual property rights to the same extent as the United States.

•

In connection with our equity line of credit, or ELOC, arrangement, we issued Lincoln Park Capital Fund, LLC 246,792 shares of our common stock.

•

Under our ELOC arrangement, we can sell up to $50,000,000 worth of our Common Stock over the thirty-six month term of the ELOC arrangement, to Lincoln Park Capital, LLC, beginning only after certain conditions set forth in the Purchase Agreement have been satisfied.

•

the announcement of new products or product enhancements by us or our competitors;

•

changes in our relationships with our licensors or other strategic partners;

•

developments concerning intellectual property rights and regulatory approvals;

•

variations in ours and our competitors’ results of operations;

•

substantial sales of shares of our common stock due to the release of lock-up agreements;

•

the announcement of clinical trial results;

•

the announcement of potentially dilutive financings;

•

changes in earnings estimates or recommendations by securities analysts;

•

changes in the structure of healthcare payment systems;

•

developments and market conditions in the pharmaceutical and biotechnology industries, including due to the COVID-19 pandemic; and

•

the results of clinical trials of APX3330, PS, or any other product candidate that we may develop.

ITEM 1B.

UNRESOLVED STAFF COMMENTS

ITEM 1C.

CYBERSECURITY

ITEM 2.

PROPERTIES

ITEM 3.

LEGAL PROCEEDINGS

ITEM 4.

MINE SAFETY DISCLOSURES

ITEM 5.

MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES

ITEM 6.

[RESERVED]

•

continue clinical trials for APX3330, PS and for any other product candidate in our future pipeline;

•

continue nonclinical studies for APX3330, APX2009 and APX2014, PS and for any other product candidate in our future pipeline;

•

develop additional product candidates that we identify, in-license or acquire;

•

seek regulatory approvals for any product candidates that successfully complete clinical trials;

•

contract to manufacture our product candidates;

•

maintain, expand and protect our intellectual property portfolio;

•

hire additional staff, including clinical, scientific, operational and financial personnel, to execute our business plan;

•

add operational, financial and management information systems and personnel to support our product development and potential future commercialization efforts;

•

continue to operate as a public company; and

•

establish on our own or with partners, a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain regulatory approval.

		For the Year Ended December 31,
		2023				2022				Change
License and collaborations revenue		$	19,049			$	39,850			$	(20,801	)
Operating expenses:
General and administrative			11,959				7,269				4,690
Research and development			17,653				14,355				3,298
Total operating expenses			29,612				21,624				7,988
(Loss) income from operations			(10,563	)			18,226				(28,789	)
Financing costs			(1,328	)			—				(1,328	)
Interest expense			—				(9	)			9
Fair value change in derivative liabilities			80				—				80
Other income (expense), net			1,837				(14	)			1,851
(Loss) income before income taxes			(9,974	)			18,203				(28,177	)
Provision for income taxes			(12	)			(315	)			303
Net (loss) income		$	(9,986	)		$	17,888			$	(27,874	)

		For the Year Ended
		December 31,
		2023				2022				Change
External costs:
Phentolamine Ophthalmic Solution 0.75% (“PS”)		$	9,983			$	8,962			$	1,021
APX 3330			4,818				3,047				1,771
Unallocated			678				647				31
Total external cost			15,479				12,656				2,823
Internal costs:
Employee related expenses			2,148				1,637				511
Facilities, supplies and other			26				62				(36	)
Total internal costs			2,174				1,699				475
Total research and development expenses		$	17,653			$	14,355			$	3,298

		For the Year Ended December 31,
		2023				2022
Net cash (used in) provided by operating activities		$	(1,112	)		$	14,314
Net cash used in investing activities			—				—
Net cash provided by financing activities			8,979				3,786
Net increase in cash and cash equivalents		$	7,867			$	18,100

ITEM 7A.

QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK

ITEM 8.

FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA

ITEM 9.

CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE

ITEM 9A.

CONTROLS AND PROCEDURES