Ocuphire Pharma, Inc. - Annual Report: 2021 (Form 10-K)

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 10-K

 

 

For the Fiscal Year Ended December 31, 2021

or

 

For the transition period from _____ to _____

 

Commission File No. 001-34079

 

Ocuphire Pharma, Inc.

(Exact name of registrant as specified in its charter)

 

Registrant’s telephone number, including area code: (248) 681-9815

 

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

 

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.

 

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 ☐    No ☒

 

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐    No ☒

 

The aggregate market value of the common equity held by non-affiliates of the registrant on June 30, 2021, based on the closing price on that date of $5.28, was approximately $83,840,460. As of March 23, 2022, there were 18,989,817 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 2022 Annual Meeting of Stockholders, to be filed subsequent to the date hereof, 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, 2021.

 

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Ocuphire Pharma, Inc.

Form 10-K

TABLE OF CONTENTS

In this Annual Report on Form 10-K, unless otherwise specified, references to “we,” “us,” “our,” “Ocuphire” or “the Company” mean Ocuphire Pharma, Inc., together with its former subsidiary OcuSub 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 fully described in “Item 1A. Risk Factors” in this Annual Report. The principal factors and uncertainties include, among others:

 

•

Ocuphire employees or its representatives may engage in misconduct or other improper activities, including violating applicable regulatory standards and requirements or engaging in insider trading, which could significantly harm Ocuphire’s business.

•

Ocuphire faces substantial competition, which may result in others discovering, developing, or commercializing products before or more successfully than it does.

•

Ocuphire lacks experience in commercializing products, which may have an adverse effect on its business.

•

If Ocuphire is unable to establish sales and marketing capabilities or enter into agreements with third parties to sell, market, and distribute its product candidates, if approved, it may not be successful in commercializing such product candidates if and when they are approved.

•

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

•

Ocuphire is unable to control all aspects of its clinical trials due to its reliance on clinical research organizations (“CROs”), contract development and manufacturing organizations (“CDMOs”) and other third parties that assist Ocuphire in conducting clinical trials.

•

Ocuphire is unable to control the supply, manufacture and testing of bulk drug substances and the formulation, testing and packaging of preclinical and clinical drug supplies of its product candidates, and will be unable to control these elements at the commercial stage, due to its reliance on third party manufacturers and analytical facilities.

•

If Ocuphire is not able to establish new collaborations on commercially reasonable terms, it may have to alter its development, manufacturing, and commercialization plans.

•

If Ocuphire is unable to obtain and maintain sufficient patent protection for its product candidates, its competitors could develop and commercialize products or technology similar or identical to those of Ocuphire, which would adversely affect Ocuphire’s ability to successfully commercialize any product candidates it may develop, its business, results of operations, financial condition and prospects.

•

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

•

Ocuphire may not be able to protect or practice its intellectual property rights throughout the world.

•

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

•

Ocuphire depends on intellectual property sublicensed from Apexian Pharmaceuticals, Inc. (“Apexian”) for its APX3330 product candidate under development and its additional pipeline candidates, and the termination of, or reduction or loss of rights under, this sublicense would harm Ocuphire’s business.

•

Ocuphire is dependent on its key personnel, and if it is not successful in attracting and retaining highly qualified personnel, it may not be able to successfully implement its business strategy.

•

Ocuphire will need to develop and expand its company and may encounter difficulties in managing this development and expansion, which could disrupt its operations.

•

The COVID-19 pandemic has and could continue to adversely impact Ocuphire’s business, including preclinical and clinical trials and regulatory approvals.

•

Ocuphire’s insurance policies are expensive and protect only from some business risk, which leaves Ocuphire exposed to significant uninsured liabilities.

•

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

•

The market price of Ocuphire common stock may fluctuate significantly.

•

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

ITEM 1.

BUSINESS

•

Advance the clinical development of Nyxol and APX3330. Ocuphire is currently conducting Phase 2 and Phase 3 registration trials of Nyxol and Phase 2b trials of APX3330 with the goal of filing a U.S. NDA in late 2022 for Nyxol for RM, and advancing APX3330 towards Phase 3 studies in the future.

•

Target Nyxol and APX3330 for large ophthalmic indications. Ocuphire believes Nyxol has therapeutic potential to improve vision performance in RM, presbyopia and NVD. Ocuphire also believes AXP3330 has potential to improve the health of the retina in patients with DR, DME, and wet age-related macular degeneration (wAMD), while reducing the burden of intravitreal injections.

•

Maintain and expand its intellectual property portfolio. Ocuphire owns all global patent rights to Nyxol with respect to its formulation, combinations, and use in multiple indications. Ocuphire also owns an exclusive worldwide sublicense for the Ref-1 Inhibitor program, including its lead 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. Ocuphire continues to explore additional opportunities to expand and extend this intellectual property protection, both in the U.S. and in other jurisdictions.

•

Maximize the global commercial value of Nyxol and APX3330. Ocuphire plans to seek commercial partners both in and outside of the United States. Alternatively, Ocuphire believes it could independently commercialize Nyxol and/or APX3330 in the United States with a targeted sales force.

•

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

•

Reduction in pupil diameter with durable effects. In multiple Phase 2 and Phase 3 trials Nyxol reduced pupil diameter by approximately ~1 – 1.5 mm in both mesopic (dim) and photopic (bright) conditions, with such reductions sustained over 24 hours. Nyxol with LDP as adjunctive eye drop provides an optimal pupil size of 2 mm – 3 mm.

•

Improvement in distance corrected near visual acuity. When studied in patients with presbyopia in Phase 2 trials, Nyxol alone and in combination with LDP showed statistically significant improvement in distance-corrected near visual acuity with ≥3 lines gain from baseline.

•

Improvement in low contrast visual acuity. When studied in patients with NVD in multiple Phase 2 trials, Nyxol showed statistically significant improvement in low contrast mesopic best-corrected distance visual acuity at ≥1 and ≥2 lines, with a trend at ≥3 lines on a standard visual chart.

•

Favorable tolerability profile. To date, Nyxol has been observed to be well-tolerated, with unchanged or decreased intraocular pressure in the nine completed Phase 1, Phase 2 and Phase 3 clinical trials conducted. Nyxol produces a transient, mild hyperemia effect that disappears within several hours or immediately upon application of anti-redness eye drops. Nyxol is also observed to have no systemic effects such as changes in blood pressure or heart rate.

•

Designed to be a convenient, once-daily eye drop or tunable combination option. Nyxol is being evaluated for chronic use as a once-daily administration before bedtime. Nyxol has been shown in multiple Phase 2 trials and a Phase 3 trial to have a durable effect of over 24 hours, which could encourage patient compliance.  Use of LDP eye drops as an adjunct to Nyxol may offer the benefit of tunability to presbyopia patients based on their vision and lifestyle needs.

•

Stable, cost-effective ophthalmic formulation. Nyxol is a single-use, preservative-free, proprietary eye drop formulation with stability suitable to support potential commercialization. Its active pharmaceutical ingredient, phentolamine mesylate USP grade, is a small molecule with advantages of standardized, scalable, and lower-cost manufacturing processes.

•

RM, the reversal of pharmacologically induced dilation of the pupils, where dilation leads to increased sensitivity to light and an inability to focus, making it difficult to read, work, and drive. RM is a single-use indication for which no approved therapy is commercially available at present.

•

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 launched in December 2021, is the only eye drop currently marketed for the treatment of presbyopia.

•

NVD, a condition in which peripheral imperfections (aberrations) of the cornea scatter light when the pupil opens wide in dim light. Patients with NVD experience glare, halos, starbursts, and decreased contrast sensitivity. NVD is a new indication with no approved therapies.

•

Potential to be the first oral therapy. Compared to frequent intravitreal anti-VEGF injections, associated with ocular complications, once or twice a day oral administration of APX3330 could be a convenient alternative treatment for retinal disease, if approved.

•

Upstream target implicated in two validated pathways. APX3330 is designed to lead to inhibition of 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.

•

Favorable tolerability profile. In 11 completed Phase 1 and Phase 2 clinical trials, APX3330 was well-tolerated with no significant acute neurologic, cardiovascular, hepatic, or pulmonary events.

•

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

•

Stable, cost-effective oral tablet. 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.

•

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.

•

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.

•

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.

•

Non-proliferative DR, or NPDR. NPDR is an earlier, more typical 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.

•

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.

Trial Name (IND Number)

​

Patient / Indication

Phase

Trial Objectives

​

Doses

Number of Patients^

​ Dosing

Key Endpoints

NYX-001 (67-288)

​

Healthy Volunteers

1

Double-masked, randomized, single dose, 3-arm controlled, parallel trial to determine the efficacy and safety of phentolamine mesylate

0.2% PMOS

Nyxol*=15, Visine=15, Visine + Nyxol*=15 Total = 45

Single-dose

Safety and Efficacy (PD)

NYX-002^ (67-288)

​

Healthy Volunteers

1

Double-masked, randomized, placebo-controlled, single-dose, incomplete block, 3-period crossover, dose escalation trial evaluating the tolerability and efficacy of phentolamine mesylate

​

0.2%, 0.4%, 0.8% PMOS

Nyxol*=16 Placebo=12 Total = 16

Single-dose

Safety and Efficacy (PD, VA)

OP-NYX-004^ (73-987)

​

Night Vision Disturbances Patients

1 / 2

Double-masked, randomized, placebo-controlled, single-dose, incomplete block 3-period crossover, dose escalation trial to determine the efficacy and safety of phentolamine mesylate

​

0.2%, 0.4%, 0.8% PMOS

Nyxol*=16 Placebo=12 Total = 16

Single-dose

Safety and Efficacy

OP-NYX-SNV (70-736)

​

Severe Night Vision Disturbances Patients

2

Double-masked, randomized, placebo-controlled, single-dose trial to assess the efficacy and safety of phentolamine mesylate ophthalmic solution

​

1.0% PMOS

Nyxol*=16, Placebo=8 Total = 24

Single-dose

Safety and Efficacy (PD, LCVA, CS, WA)

OP-NYX-01a2 (70-499)

​

Severe Night Vision Disturbances Patients

2

Double-masked, randomized, placebo-controlled, single-dose, 3-arm trial to assess the efficacy and safety of Nyxol

0.5%, 1.0% PMOS

Nyxol=40 Placebo=20 Total = 60

Multiple doses (15-28 days)

Safety and Efficacy (PD, LCVA, CS)

OPI-NYXG-201 (ORION-1) (70-499)

​

Glaucoma and Ocular Hypertension, Elderly Patients

2b

Double-masked, randomized, placebo-controlled, multiple-dose, multi-center trial to assess the efficacy and safety of Nyxol

​

1.0% PMOS

Nyxol=19 Placebo=20 Total = 39

Multiple doses (14 days)

Safety and Efficacy (IOP, PD, near VA, VA)

OPI- NYXRM-201 (MIRA-1) (70-499)

​

Healthy Patients/ Reversal of Mydriasis

2b

Double-masked, randomized, placebo-controlled, crossover, single-dose, multi-center trial to assess the efficacy and safety of Nyxol in reducing pharmacologically induced mydriasis

1.0% PMOS

Nyxol=31 Placebo=32 Total = 32

Single-dose

Safety and Efficacy (PD, Accommodation, VA)

OPI- NYXRM-301 (MIRA-2) (70-499)

​

Healthy Patients/ Reversal of Mydriasis (including 12–17 years-old)

3

Double-masked, randomized, placebo-controlled, single-dose, multi-center trial to assess the efficacy and safety of Nyxol in reducing pharmacologically induced mydriasis

0.75% POS

Nyxol=94 Placebo=91 Total = 185

Single-dose

Safety and Efficacy (PD, Accommodation, VA)

OPI-NYXRM-302 (MIRA-3) (70-499)

Healthy Patients/ Reversal of Mydriasis (including 12-17-years old)

Double-masked, randomized, placebo-controlled, single-dose, multi-center trial to assess the efficacy and safety of Nyxol in reducing pharmacologically induced mydriasis

0.75% POS

Pending data Total = 368

Single-dose

Safety and Efficacy (PD, Accommodation, VA)

OPI-NYXRMP-303 (MIRA-4) (70-499)

Healthy Patients/ Reversal of Mydriasis (between ages of 3-and 11)

Randomized, Parallel-Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically Induced Mydriasis in Healthy Pediatric Subjects

0.75% POS

Pending data Total = 23

Single-dose

Safety and Efficacy (PD)

OPI-NYXP-201 (VEGA-1) (70-499)

Presbyopia patients (ages of 40 and 64)

2

Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) with Low-Dose (0.4%) Pilocarpine Eye Drops in Subjects with Presbyopia

0.75% POS

Nyxol +LDP = 44 Placebo alone = 45 Nyxol  alone  = 30 Placebo +LDP = 31

Multiple doses (up to 4 days), Single dose of LDP

Safety and Efficacy (DCNVA, VA, PD)

OPI-NYXDLD-301 (LYNX-1) (70-499)

Night Vision Disturbances in adults

Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects with Dim Light Vision Disturbances

0.75%  POS

Pending data Total =145

Multiple doses (14 days)

Safety and Efficacy (mLCVA, VA, PD)

Trial Number / Name

​

Patient / Indication

​

Phase

​Trial Objectives

​Doses

Number of Patients^

APX3330 Total Exposure Days

Dosing

​

Key Endpoints

APX_CLN_0001 (Eisai) Completed

​

Healthy Volunteers

​

1

​Single-dose placebo-controlled trial of APX3330 to investigate safety and pharmacokinetics

​10 mg 30 mg 60 mg 120 mg 180 mg 240 mg

APX3330 = 12 Placebo = 6

36 days

Single dose

​

Plasma Concentration of total quinone forms, safety

APX_CLN_0002 (Eisai) Completed

​

Healthy Volunteers

​ 1

Repeat-dose placebo-controlled trial to investigate safety and pharmacokinetics

​

120 mg QD 120 mg BID

​

APX3330 = 12 Placebo = 6

96 days

8 days

​

Plasma Concentration of APX3330, safety

APX_CLN_0003 (Eisai) Completed

​

Healthy Volunteers

​1

Repeat-dose trial to determine effects of food on pharmacokinetics

​

240 mg

​

APX3330 = 6

84 days

1 week

​

Plasma Concentration of APX3330, safety

APX_CLN_0004 (Eisai) Completed

​

Healthy Volunteers

​1

Single-dose trial to determine the effects of meals on pharmacokinetics

​

120 mg

​

APX3330 = 6

6 days

Single dose

​

Plasma Concentration of APX3330, Safety

APX_CLN_0005 (Eisai) Completed

​

Chronic Hepatitis B Patients

​2

Dose-escalation trial to investigate safety, efficacy and tolerability

​

20 mg 60 mg 120 mg 240 mg

​

APX3330 = 40

3360 days

12 weeks

​

Safety

APX_CLN_0006 (Eisai) Completed

​

Chronic Hepatitis C Patients

​2

Dose-escalation trial to investigate safety, efficacy and tolerability

​

20 mg 60 mg 120 mg 240 mg

​

APX3330 = 51

4284 days

12 weeks

​

Safety

APX_CLN_0007 (Eisai) Completed

Chronic Hepatitis C Patients

​

2

Double-masked, placebo-controlled trial to investigate safety, efficacy and tolerability

120 mg 240 mg

​

APX3330 = 128   Placebo = 68

​

10,752 days

​

Placebo = 82 days   APX3330 120 mg = 79 days   240 mg = 78 days

Rate of change in GPT level, improvement in liver function, general performance

APX_CLN_0008^ (Eisai) Completed

Healthy Patients

​

1

Single-blind, single-dose, 3-step trial to investigate safety and pharmacokinetics of higher doses

300 mg 420 mg 600 mg

​

APX3330 = 18

​

54 days

​

Single dose

Plasma Concentration of APX3330, safety

APX_CLN_0009 (Eisai) Completed

Advanced Liver Cirrhosis Patients

​

2

Repeated-dose trial to investigate safety, efficacy and tolerability

120 mg

​

APX3330 = 30

​

420 days

​

2 weeks

Liver function, patient functional status, tolerability

APX_CLN_0010 (Eisai) Completed

Advanced Liver Cirrhosis Patients

​

2

Repeated-dose trial to investigate safety, efficacy and tolerability

120 mg

​

APX3330 = 18

​

504 days

​

4 weeks

Liver function, patient functional status, tolerability

APX_CLN_0011 (Apexian) Completed

Advanced Solid Tumor Patients

​

1

Multicenter, open-label, dose-escalation to investigate safety, efficacy, pharmacokinetics, and recommended Phase 2 dose

240 mg 360 mg 480 mg 600 mg 720 mg

​

APX3330 = 19

​

2354 days

​

21-day cycles until disease progression or study withdrawal

Tumor response, safety, PK, target engagement

ZETA-1 (Ocuphire) Ongoing, Masked

Diabetic Retinopathy and DME

2

Double-masked, randomized, placebo-controlled, multi-center trial

600mg

Pending data N= 103 APX3330 Placebo

>3,700 (estimated Jan 2022)

600mg daily for 24 weeks

≥ 2 step improvement on the DRSS score at week 24

•

CSF-1, with low dose pilocarpine and a secondary agent (lubricant), developed by Orasis Pharmaceuticals Ltd.

•

LNZ100 and LNZ101, with aceclidine (another miotic agent) and brimonidine, developed by Lenz Therapeutics.

•

MicroLine®, which is a micro-dose delivery of pilocarpine using proprietary device developed by Eyenovia, Inc.

•

KT-101, which uses pilocarpine in the AcuStream delivery system, developed by Kedalion Therapeutics, Inc.

•

BrimocholTM, with brimonidine and carbachol (both are miotic agents), developed by Visus Therapeutics, Inc.

•

UNR844, which uses a mechanism that involves softening the lens to increase near visual acuity, developed by Novartis AG (originally Encore Vision, Inc.).

•

Lucentis® (ranibizumab) and Avastin® (bevacizumab), which are anti-VEGF monoclonal antibody intravitreal injections, developed by Genentech, Inc and Roche AG.

•

EYLEA® (aflibercept), a VEGF inhibitor intravitreal injection, developed by Regeneron Pharmaceuticals.

•

Vabysmo® (Faricimab), a bispecific monoclonal antibody targeting VEGF-A and Ang-Tie2 pathway developed by Genentech, Inc and Roche AG.

•

Beovu® (Brolucizumab), an anti-VEGF monoclonal antibody intravitreal injection, developed by Novartis AG.

•

MACUGEN® (pegaptanib sodium injection), a selective inhibitor of VEGF-165, developed by Bausch + Lomb.

•

Ozurdex® (dexamethasone), a corticosteroid IVT implant, developed by Allergan plc.

•

Iluvien (fluocinolone acetonide), a corticosteroid IVT implant, developed by Alimera Sciences, Inc.

•

Abicipar, an anti-VEGF intravitreal injection with a long duration of action, developed by Allergan plc and Molecular Partners.

•

KSI-301, an anti-VEGF antibody intravitreal injection coupled with a biopolymer that is intended to increase the time between injections, developed by Kodiak Sciences.

•

OPT-302, an intravitreal injection which binds to multiple types of VEGF receptors that could be used with other anti-VEGF agents, developed by Opthea Limited.

•

ALG-1001, an integrin peptide therapy intravitreal injection that is being evaluated as a sequential or in-combination therapy with bevacizumab in patients with DME, developed by Allegro Ophthalmics, LLC.

•

RG-7774, an orally administered selective CB2 (Cannabinoid 2) receptor agonist that is being evaluated in patients with moderately severe to severe non-proliferative diabetic retinopathy, developed by Hoffmann-LA Roche, AG.

•

RZ402, an oral small molecule selective and potent plasma kallikrein inhibitor (PKI) for the chronic treatment of diabetic macular edema (DME), developed by Rezolute, Inc.

•

Xiflam™, an oral small molecule drug for the treatment of dry form of Age-Related Macular Degeneration (AMD), Geographic Atrophy (GA), Diabetic Retinopathy (DR) manifesting Diabetic Macular Edema (DME), developed by InflammX.

•

AKST4290, an oral small molecule CCR3 Eotaxin inhibitor for the treatment of diabetic retinopathy and wet AMD.

•

BAY1101042, an oral guanylate cycles activator for the treatment of diabetic retinopathy.

•

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;

•

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

•

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

•

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

•

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;

•

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

•

preparation and submission to the FDA of an NDA;

•

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

•

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;

•

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

•

payment of user fees and securing FDA approval of the NDA; and

•

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

•

Phase 1. The drug is initially introduced into healthy human patients 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.

•

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.

•

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.

•

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

•

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

•

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

•

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

•

injunctions or the imposition of civil or criminal penalties.

•

the federal Anti-Kickback Statute, which 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;

•

the federal civil and criminal false claims laws, including the civil False Claims Act, and civil monetary penalties laws, which prohibit individuals or entities from, among other things, knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

•

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional federal criminal laws that prohibit, among other things, knowingly and willingly executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

•

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, which also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

•

the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies to report specially to the Centers for Medicare & Medicaid Services, or CMS, within the U.S. Department of Health and Human Services, information related to payments and other transfers of value to clinicians and teaching hospitals and clinician ownership and investment interests; and

•

analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to healthcare items or services that are reimbursed by non-governmental third-party payors, including private insurers.

•

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;

•

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;

•

expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program 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 Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;

•

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

•

established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50% point-of-sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare Part D;

•

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

•

the Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to the Medicare program to reduce expenditures by the program that could result in reduced payments for prescription drugs. However, the IPAB implementation has not been clearly defined. The ACA provided that under certain circumstances, IPAB recommendations will become law unless Congress enacts legislation that will achieve the same or greater Medicare cost savings; and

•

established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

ITEM 1A.

RISK FACTORS

•

the data collected from preclinical studies and clinical trials of Ocuphire’s product candidates may not be sufficient to support the submission of an NDA;

•

Ocuphire may not be able to demonstrate to the satisfaction of the FDA that its product candidates are safe and effective for any indication;

•

the results of clinical trials may not meet the level of statistical significance or clinical significance required by the FDA for approval;

•

the FDA may disagree with the number, design, size, conduct, or implementation of Ocuphire’s clinical trials;

•

the FDA may not find the data from preclinical studies and clinical trials sufficient to demonstrate that Ocuphire’s product candidates’ clinical and other benefits outweigh the safety risks;

•

the FDA may disagree with Ocuphire’s interpretation of data from preclinical studies or clinical trials;

•

the FDA may not accept data generated at Ocuphire’s clinical trial sites;

•

the FDA may have difficulties scheduling an advisory committee meeting in a timely manner or the advisory committee may recommend against approval of Ocuphire’s application or may recommend that the FDA require, as a condition of approval, additional preclinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions;

•

the FDA may require development of a Risk Evaluation and Mitigation Strategy (REMS) as a condition of approval;

•

the FDA may identify deficiencies in the manufacturing processes or facilities of third-party manufacturers with which Ocuphire enters into agreements for clinical and commercial supplies; or

•

the FDA may change its approval policies or adopt new regulations.

•

regulators or IRBs may not authorize Ocuphire or its investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site including due to the ongoing COVID-19 pandemic or other public health emergency;

•

government or regulatory delays and changes in regulatory requirements, policy and guidelines may require Ocuphire to perform additional clinical trials or use substantial additional resources to obtain regulatory approval, including due to the ongoing COVID-19 pandemic or other public health emergency;

•

Ocuphire may have delays in reaching or fail to reach agreement on acceptable clinical trial contracts or clinical trial protocols with prospective trial sites, including due to the ongoing COVID-19 pandemic or other public health emergency;

•

clinical trials may produce negative or inconclusive results, and Ocuphire may decide, or regulators may require it, to conduct additional clinical trials or abandon product development programs, including due to the ongoing COVID-19 pandemic or other public health emergency;

•

the number of patients required for clinical trials may be larger, enrollment in these clinical trials may be slower or participants may drop out of these clinical trials at a higher rate than Ocuphire anticipates, including due to the ongoing COVID-19 pandemic or other public health emergency;

•

Ocuphire’s third-party contractors may fail to comply with regulatory requirements or meet their contractual obligations to Ocuphire in a timely manner, or at all;

•

Ocuphire’s patients or medical investigators may be unwilling to follow its clinical trial protocols;

•

Ocuphire might have to suspend or terminate clinical trials for various reasons, including a finding that the participants are being exposed to unacceptable health risks;

•

the cost of clinical trials may be greater than Ocuphire anticipates, including due to the ongoing COVID-19 pandemic or other public health emergency;

•

the supply or quality of any product candidate or other materials necessary to conduct clinical trials may be insufficient or inadequate;

•

the product candidate may have undesirable side effects or other unexpected characteristics, causing Ocuphire or its investigators, regulators or IRBs to suspend or terminate the trials;

•

clinical trials may be delayed or terminated because of the ongoing COVID-19 pandemic or another public health emergency; and

•

federal agencies may, due to reduced manpower or diverted resources to the COVID-19 pandemic, require more time to review clinical trial protocols and INDs.

•

severity of the disease under investigation;

•

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

•

eligibility criteria for the trial in question;

•

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

•

its payments for conducting clinical trials;

•

perceived risks and benefits of the product candidate under study;

•

efforts to facilitate timely enrollment in clinical trials;

•

patient referral practices of physicians;

•

the ability to monitor patients adequately during and after treatment;

•

proximity and availability of clinical trial sites for prospective patients;

•

the ability of patients to safely participate in clinical trials during the COVID-19 pandemic or other public health emergencies; and

•

the ability to monitor patients adequately during periods in which social distancing is required or recommended due to the COVID-19 pandemic.

•

regulatory authorities may withdraw their approval of the product;

•

Ocuphire 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);

•

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

•

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

•

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

•

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

•

Ocuphire’s reputation may suffer generally both among clinicians and patients.

•

obtain favorable results from and complete the clinical development of both Nyxol and APX3330 for their planned indications, including successful completion of additional clinical trials for these indications;

•

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

•

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 product candidates that we develop, if approved;

•

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

•

address any competing products and technological and market developments;

•

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

•

achieve market acceptance of its product candidates.

•

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

•

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

•

the number and characteristics of any additional product candidates it develops or acquires, if any;

•

Ocuphire’s ability to establish and maintain collaborations on favorable terms, if at all;

•

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

•

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

•

the cost of manufacturing its product candidates or products Ocuphire successfully commercializes; and

•

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

•

litigation involving patients taking Ocuphire’s drugs;

•

restrictions on such drugs, manufacturers, or manufacturing processes;

•

restrictions on the labeling or marketing of a drug;

•

restrictions on drug distribution or use;

•

requirements to conduct post-marketing studies or clinical trials;

•

warning letters or untitled letters;

•

withdrawal of the drugs from the market;

•

refusal to approve pending applications or supplements to approved applications that Ocuphire submits;

•

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

•

fines, restitution, or disgorgement of profits or revenues;

•

suspension or withdrawal of marketing approvals;

•

damage to relationships with any potential collaborators;

•

unfavorable press coverage and damage to Ocuphire’s reputation;

•

refusal to permit the import or export of drugs;

•

product seizure; or

•

injunctions or the imposition of civil or criminal penalties.

•

the federal Anti-Kickback Statute 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, or in return for, either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;

•

the federal false claims and civil monetary penalties laws, including the civil False Claims Act, impose criminal and civil penalties, including civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government;

•

HIPAA imposes criminal and civil liability for, among other things, executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

•

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and its implementing regulations, also imposes obligations, including mandatory contractual terms, on certain people and entities with respect to safeguarding the privacy, security, and transmission of individually identifiable health information;

•

the federal Physician Payments Sunshine Act under the Affordable Care Act 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, with specific exceptions, to report specially to the Centers for Medicare & Medicaid Services within the U.S. Department of Health and Human Services information related to physician payments and other transfers of value and physician ownership and investment interests; and

•

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. Certain state and foreign laws also govern the privacy and security of health information in ways that differ from each other and often are not preempted by HIPAA, thus complicating compliance efforts.

•

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 Ocuphire.

•

CSF-1, with low dose pilocarpine and a secondary agent (lubricant), developed by Orasis Pharmaceuticals Ltd.

•

LNZ100 and LNZ101, with aceclidine (another miotic agent), developed by Lenz Therapeutics.

•

MicroLine®, which is a micro-dose delivery of pilocarpine using proprietary device developed by Eyenovia, Inc.

•

KT-101, which uses pilocarpine in the AcuStream delivery system, developed by Kedalion Therapeutics, Inc.

•

Brimochol™, with brimonidine and carbachol (both are miotic agents), developed by Visus Therapeutics, Inc.

•

UNR844, which uses a mechanism that involves softening the lens to increase near visual acuity, developed by Novartis AG (originally Encore Vision, Inc.).

•

Lucentis® (ranibizumab) and Avastin® (bevacizumab), which are anti-VEGF monoclonal antibody intravitreal injections, developed by Genentech, Inc and Roche AG.

•

EYLEA® (aflibercept), a VEGF inhibitor intravitreal injection, developed by Regeneron Pharmaceuticals.

•

Vabysmo® (Faricimab), a bispecific monoclonal antibody targeting VEGF-A and Ang-Tie2 pathway developed by Genentech, Inc and Roche AG.

•

Beovu® (Brolucizumab), an anti-VEGF monoclonal antibody intravitreal injection, developed by Novartis AG.

•

MACUGEN® (pegaptanib sodium injection), a selective inhibitor of VEGF-165, developed by Bausch + Lomb.

•

Ozurdex® (dexamethasone), a corticosteroid IVT implant, developed by Allergan plc.

•

Iluvien (fluocinolone acetonide), a corticosteroid IVT implant, developed by Alimera Sciences, Inc

•

Abicipar, an anti-VEGF intravitreal injection with a long duration of action, developed by Allergan plc and Molecular Partners.

•

KSI-301, an anti-VEGF antibody intravitreal injection coupled with a biopolymer that is intended to increase the time between injections, developed by Kodiak Sciences.

•

OPT-302, an intravitreal injection which binds to multiple types of VEGF receptors that could be used with other anti-VEGF agents, developed by Opthea Limited.

•

ALG-1001, an integrin peptide therapy intravitreal injection that is being evaluated as a sequential or in-combination therapy with bevacizumab in patients with DME, developed by Allegro Ophthalmics, LLC.

•

RG-7774, an orally administered selective CB2 (Cannabinoid 2) receptor agonist that is being evaluated in patients with moderately severe to severe non-proliferative diabetic retinopathy, developed by Hoffmann-LA Roche, AG.

•

RZ402, a small molecule selective and potent plasma kallikrein inhibitor (PKI) for the chronic treatment of diabetic macular edema (DME), developed by Rezolute, Inc.

•

Xiflam™, an oral small molecule drug for the treatment of dry form of Age-Related Macular Degeneration (AMD), Geographic Atrophy (GA), Diabetic Retinopathy (DR) manifesting Diabetic Macular Edema (DME), developed by InflammX.

•

AKST4290, an oral small molecule CCR3 Eotaxin inhibitor for the treatment of diabetic retinopathy and wet AMD.

•

BAY1101042, an oral guanylate cycles activator for the treatment of diabetic retinopathy.

•

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 persuade adequate numbers of physicians to prescribe its product candidate;

•

the lack of complementary products to be offered by sales personnel, which may put Ocuphire 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 it enters into arrangements with third parties to perform sales, marketing, and distribution services, Ocuphire’s product revenues or the profitability of these product revenues to it are likely to be lower than if it were to market and sell a product that Ocuphire developed itself. In addition, Ocuphire 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 it. Ocuphire 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 Ocuphire does not establish sales and marketing capabilities successfully, either on its own or in collaboration with third parties, it will not be successful in commercializing its product candidates.

•

efficacy and potential advantages compared to alternative treatments;

•

the ability to offer Ocuphire’s 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 Ocuphire’s product together with other medications;

•

interactions of its product with other medicines patients are taking;

•

inability of certain types of patients to take Ocuphire’s 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 Ocuphire’s sales and marketing strategies;

•

Ocuphire’s 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;

•

Ocuphire’s 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 Ocuphire is developing;

•

injury to Ocuphire’s 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 Ocuphire’s primary business;

•

loss of revenue; and

•

the inability to commercialize any product candidate that Ocuphire may develop.

•

have staffing difficulties;

•

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 Ocuphire’s 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 its 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 Ocuphire’s;

•

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 Ocuphire’s intellectual property rights or may use its proprietary information in such a way as to invite litigation that could jeopardize or invalidate Ocuphire’s proprietary information or expose Ocuphire to litigation;

•

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

•

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

•

Ocuphire may lose certain valuable rights under circumstances identified in its collaborations, including if it undergoes 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 Ocuphire’s discoveries and use this knowledge to compete with Ocuphire in the future;

•

the results of collaborators’ preclinical 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 Ocuphire’s collaborations could adversely affect its attractiveness to potential future collaborators or acquirers;

•

collaboration agreements may not lead to development or commercialization of its product candidate in the most efficient manner or at all. If a present or future collaborator of Ocuphire were to be involved in a business combination, the continued pursuit and emphasis on its 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 Ocuphire’s equity securities which would result in dilution to Ocuphire 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 Ocuphire’s 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 Ocuphire’s 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

•

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

•

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

•

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

•

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

•

Ocuphire was the first to make the inventions covered by each of its patents and pending patent applications;

•

Ocuphire was the first to file patent applications for these inventions;

•

others will not develop similar or alternative technologies that do not infringe Ocuphire’s patents;

•

any of Ocuphire’s patents will be valid and enforceable;

•

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

•

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

•

that Ocuphire’s 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 Ocuphire’s 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 Ocuphire’s collaborative development relationships;

•

Ocuphire’s 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 its product candidates;

•

different medical practices and customs affecting acceptance of its 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 its 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.

•

the announcement of new products or product enhancements by Ocuphire or its competitors;

•

changes in Ocuphire’s relationships with its licensors or other strategic partners;

•

developments concerning intellectual property rights and regulatory approvals;

•

variations in Ocuphire’s and Ocuphire’s 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; and

•

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

ITEM 1B.

UNRESOLVED STAFF COMMENTS

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]

ITEM 7.

MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

		For the Year Ended December 31,
		2021				2020				Change
Collaborations revenue		$	589			$	—			$	589
Operating expenses:
General and administrative			8,121				2,818				5,303
Research and development			15,173				6,648				8,525
Acquired in‑process research and development			—				10,502				(10,502	)
Total operating expenses			23,294				19,968				3,326
Loss from operations			(22,705	)			(19,968	)			(2,737	)
Interest expense			(2	)			(6,847	)			6,845
Fair value change in derivative and warrant liabilities			(33,829	)			(1,486	)			(32,343	)
Gain on note extinguishment			—				3,672				(3,672	)
Other (expense) income, net			(157	)			9				(166	)
Loss before income taxes			(56,693	)			(24,620	)			(32,073	)
Provision for income taxes			—				—				—
Net loss		$	(56,693	)		$	(24,620	)		$	(32,073	)

•

continued clinical trials and preclinical studies for Nyxol, APX 3330 and for any other product candidate in its future pipeline;

•

developing additional product candidates that it identifies, in-licenses or acquires;

•

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

•

contracts to manufacture its product candidates;

•

establishing on its own or with partners, a sales, marketing and distribution infrastructure to commercialize any products for which it may obtain regulatory approval;

•

maintaining, expanding and protecting its intellectual property portfolio;

•

hiring additional staff, including clinical, scientific, operational and financial personnel, to execute its business plan;

•

adding operational, financial and management information systems and personnel, including personnel to support its product development and potential future commercialization efforts; and

•

operating as a public company.

•

Qualified Financing or IPO: An amount of shares of Ocuphire common stock equal to 135% of the Note Value divided by the per share price of Ocuphire common stock issued to purchasers in the Qualified Financing or IPO.

•

CIC: An amount of shares of Ocuphire common stock equal to 200% of the Note Value divided by the per share price of Ocuphire common stock based on the valuation of such CIC.

•

Reverse Merger: Either (i) shares of Ocuphire common stock issued in the Reverse Merger or (ii) equity securities of the Reverse Merger counterparty, in an amount equal to 135% of the Note Value divided by the per share price at which such shares were issued to either stockholders of Ocuphire or stockholders of the Reverse Merger counterparty.

•

IPO: An amount of shares of Ocuphire common stock equal to the greater of: (i) 150% of the Note Value divided by the per share price of Ocuphire common stock issued to purchasers in the IPO, and (ii) 100% of the Note Value divided by the per share price of $10.37.

•

CIC: An amount of shares of Ocuphire common stock equal to the greater of: (i) 200% of the Note Value divided by the per share price of Ocuphire common stock based on the valuation of such CIC, and (ii) 100% of the Note Value divided by the per share price of $10.37.

•

Qualified Financing: An amount of shares of Ocuphire common stock equal to 150% of the Note Value divided by the per share price of Ocuphire common stock issued to purchasers in the Qualified Financing.

•

Reverse Merger: Either shares of Ocuphire common stock issued in the Reverse Merger or equity securities of the Reverse Merger counterparty, in an amount equal to the greater of: (i) 150% of the Note Value divided by the per share price at which such shares were issued to either stockholders of Ocuphire or stockholders of the Reverse Merger counterparty, and (ii) 100% Note Value divided by the per share price of $10.37.

		For the Year Ended December 31,
		2021				2020
Net cash used in operating activities		$	(19,370	)		$	(6,797	)
Net cash (used in) provided by investing activities			(100	)			539
Net cash provided by financing activities			27,605				21,120
Net increase in cash and cash equivalents		$	8,135			$	14,862

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

ITEM 9B.

OTHER INFORMATION

ITEM 9C.

DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS

ITEM 10.

DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE

ITEM 11.

EXECUTIVE COMPENSATION

ITEM 12.

SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS

ITEM 13.

CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE

ITEM 14.

PRINCIPAL ACCOUNTANT FEES AND SERVICES

ITEM 15.

EXHIBITS, FINANCIAL STATEMENT SCHEDULES

EXHIBIT NUMBER	​	DESCRIPTION OF DOCUMENT
2.1+	​	Agreement and Plan of Merger, dated as of June 17, 2020, by and among the Registrant, Razor Merger Sub, Inc. and Ocuphire Pharma, Inc. (incorporated by reference to Exhibit 2.1 to the Registrant’s Current Report on Form 8-K, filed on June 19, 2020)..
2.2	​	First Amendment to Agreement and Plan of Merger and Reorganization, dated as of June 29, 2020, by and among Rexahn, Merger Sub and Ocuphire (incorporated by reference to Exhibit 2.1 to the Registrant’s Current Report on Form 8-K , filed on July 1, 2020).
3.1	​	Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference to Appendix G to the Registrant’s Definitive Proxy Statement on Schedule 14A, filed on April 29, 2005).
3.2	​	Certificate of Amendment of Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed on May 5, 2017).
3.3	​	Certificate of Amendment of Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed on August 30, 2018).
3.4	​	Certificate of Amendment of Amended and Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed on April 12, 2019).
3.5	​	Certificate of Amendment of Amended and Restated Certificate of Incorporation (incorporated by reference to Exhibit 3.1 to the Registrant’s Current Report on Form 8-K, filed on November 6, 2020).
3.6	​	Certificate of Amendment of Amended and Restated Certificate of Incorporation (incorporated by reference to Exhibit 3.2 to the Registrant’s Current Report on Form 8-K, filed on November 6, 2020).
3.7	​	Second Amended and Restated Bylaws of the Registrant (incorporated by reference to Exhibit 3.3 to the Registrant’s Current Report on Form 8-K, filed on November 6, 2020).

4.1	​	Specimen Certificate for the Registrant’s Common Stock, par value $.0001 per share (incorporated by reference to Exhibit 4.3 to the Registrant’s Registration Statement on Form S-8 (File No. 333-129294), filed on October 28, 2005).
4.2	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on November 6, 2015).
4.3	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on February 26, 2016).
4.4	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on September 14, 2016).

4.5	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on June 7, 2017).
4.6	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on October 13, 2017).
4.7	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on October 19, 2018).
4.8	​	Form of Common Stock Purchase Warrant (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on January 25, 2019).
4.9	​	Stockholders Agreement, dated as of April 10, 2018, among Ocuphire Pharma, Inc. and Stockholders as defined therein (incorporated by reference to Exhibit 4.9 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
4.10	​	Form of Series A/B Warrants (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K, filed on July 1, 2020).
4.11	​	Description of Securities (incorporated by reference to Exhibit 4.11 to the Registrant’s Annual Report on Form 10-K, filed on March 11, 2021).
4.12		Form of Warrant to purchase shares of common stock (incorporated by reference to Exhibit 4.1 to the Registrant’s Current Report on Form 8-K/A, filed on June 7, 2021).
10.1*++	​	Amended and Restated Employment Agreement by and among the Company and Mina Sooch, effective as of November 5, 2020 (incorporated by reference to Exhibit 10.27 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.2*	​	Amended and Restated Employment Agreement by and among the Company and Bernhard Hoffmann, effective as of November 5, 2020 (incorporated by reference to Exhibit 10.29 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.3*	​	Form of Indemnification Agreement (incorporated by reference to Exhibit 10.30 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).

10.4++	​	Sublicense Agreement, dated as of January 21, 2020, by and between Ocuphire Pharma, Inc. and Apexian Pharmaceuticals, Inc (incorporated` by reference to Exhibit 10.31 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.4.1	​	First Amendment to Sublicense Agreement, dated as of June 4, 2020, by and between Apexian Pharmaceuticals, Inc. and Ocuphire Pharma, Inc (incorporated by reference to Exhibit 10.32 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.5	​	Lease Agreement, dated as of May 19, 2019, by and between Ocuphire Pharma, Inc. and Duke & Duke, LP (incorporated by reference to Exhibit 10.33 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.5.1	​	First Amendment to Lease Agreement, dated as of October 29, 2019, by and between Ocuphire Pharma, Inc. and Duke & Duke, LP (incorporated by reference to Exhibit 10.34 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.5.2		Second Lease Amendment, dated as of November 17, 2020, by and between the Company and Duke & Duke (incorporated by reference to Exhibit 10.43 to the Registrant’s Annual Report on Form 10-K, filed on March 11, 2021)
10.5.3		Third Lease Amendment, dated as of September 9, 2021, by and between the Company and Duke & Duke. (incorporated by reference to Exhibit 10.1 to the Registrant’s Quarterly Report on Form 10-Q, filed on November 12, 2021)
10.6*	​	Ocuphire Pharma, Inc. 2018 Equity Incentive Plan, dated as of April 9, 2018 (incorporated by reference to Exhibit 10.35 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.6.1*	​	First Amendment to 2018 Equity Incentive Plan, dated as of December 23, 2019 (incorporated by reference to Exhibit 10.36 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).

10.7*	​	Ocuphire Pharma, Inc. 2020 Equity Incentive Plan (incorporated by reference to Exhibit 10.38 to the Registrant’s Registration Statement on Form S-4 (File No. 333-239702), filed on September 30, 2020).
10.8	​	Contingent Value Rights Agreement, dated as of November 5, 2020, by and among the Company, Shareholder Representative Services LLC and the Olde Monmouth Stock Transfer Co., Inc. (incorporated by reference to Exhibit 10.4 to the Registrant’s Current Report on Form 8-K, filed on November 6, 2020).
10.9*	​	Ocuphire Pharma, Inc. 2021 Inducement Plan (incorporated by reference to Exhibit 10.41 to the Registrant’s Annual Report on Form 10-K, filed on March 11, 2021)
10.10*	​	Employment Agreement dated November 11, 2020, by and between the Company and Amy Rabourn (incorporated by reference to Exhibit 10.42 to the Registrant’s Annual Report on Form 10-K, filed on March 11, 2021)
10.11		Capital on Demand™ Sales Agreement, dated March 11, 2021 between the Company and JonesTrading Institutional Services LLC (incorporated by reference to Exhibit 1.1 to the Registrant’s Current Report on Form 8-K, filed on March 11, 2021).
10.12		Form of Securities Purchase Agreement, dated as of June 4, 2021, by and among Ocuphire Pharma, Inc. and the purchasers identified on the signature pages thereto (incorporated by reference to Exhibit 10.1 to the Registrant’s Current Report on Form 8-K/A, filed on June 7, 2021).
10.13		Processa License Agreement dated June 16, 2021 (incorporated by reference to Exhibit 10.1 to the Registrant’s Current Report on Form 8-K, filed on June 23, 2021).
21.1	​	Subsidiaries of the Registrant
23.1	​	Consent of Ernst & Young, LLP.
31.1	​	Certification of Principal Executive Officer pursuant to Rules 13a-14(a) and 15d-14(a) promulgated under the Securities Exchange Act of 1934, as adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002
31.2	​	Certification of Principal Financial Officer pursuant to Rules 13a-14(a) and 15d-14(a) promulgated under the Securities Exchange Act of 1934, as adopted pursuant to section 302 of the Sarbanes-Oxley Act of 2002

32.1	​	Certification of Principal Executive Officer and Principal Financial Officer pursuant to Rules 13a-14(b) and 15d-14(b) promulgated under the Securities Exchange Act of 1934 and 18 U.S.C. Section 1350, as adopted pursuant to section 906 of The Sarbanes-Oxley Act of 2002
101.INS		Inline XBRL Instance Document (the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document).
101.SCH		Inline XBRL Taxonomy Extension Schema Document
101.CAL		Inline XBRL Taxonomy Extension Calculation Linkbase Document
101.DEF		Inline XBRL Taxonomy Extension Definition Linkbase Document
101.LAB		Inline XBRL Taxonomy Extension Label Linkbase Document
101.PRE		Inline XBRL Taxonomy Extension Presentation Linkbase Document
104		Cover Page Interactive Data File (formatted as inline XBRL and contained in Exhibit 101)

+	Certain schedules and exhibits have been omitted pursuant to Item 601(b)(2) of Regulation S-K. A copy of any omitted schedule and/or exhibit will be furnished to the SEC upon request.

++	Portions of this exhibit have been omitted in compliance with Item 601 of Regulation S-K.

ITEM 16.

FORM 10-K SUMMARY