Form 8-K - Current report

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 8-K

CURRENT REPORT

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

Date of Report (Date of Earliest Event Reported): August 1, 2023

Ocuphire Pharma, Inc.

(Exact name of registrant as specified in its charter)

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

37000 Grand River Avenue, Suite 120 Farmington Hills, MI 48335

(Address of principal executive offices and zip code)

248-957-9024

(Registrant’s telephone number including area code)

(Registrant’s former name or former address, if changed since last report)

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

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

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

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

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

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

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

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

Emerging Growth Company ☐

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

Item 7.01

Regulation FD Disclosure.

On August 1, 2023, the Company posted an updated corporate presentation to its website at https://ir.ocuphire.com/presentations, which the Company may use from time to time in communications or conferences. A copy of the corporate presentation is attached as Exhibit 99.1 to this Report.

The information in this Report, including Exhibit 99.1 hereto, is furnished pursuant to Item 7.01 and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such a filing. The Company’s submission of this Report shall not be deemed an admission as to the materiality of any information required to be disclosed solely to satisfy the requirements of Regulation FD.

Exhibit 99.1 hereto contains forward-looking statements within the meaning of the federal securities laws. These forward-looking statements are based on current expectations and are not guarantees of future performance. Further, the forward-looking statements are subject to the limitations listed in Exhibit 99.1 and in the other reports of the Company filed with the Securities and Exchange Commission, including that actual events or results may differ materially from those in the forward-looking statements.

Item 9.01

Financial Statements and Exhibits.

(d)

Exhibits

Exhibit Number		Exhibit Description
99.1		Corporate Presentation, dated August 1, 2023
104		Cover Page Interactive Data File (embedded within Inline XBRL document).

SIGNATURES

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

	OCUPHIRE PHARMA, INC.


Date: August 1, 2023	By:	/s/ Richard J. Rodgers
		Richard J. Rodgers
		Interim President and Chief Executive Officer

Exhibit 99.1

Restore Vision & Clarity Ocuphire Corporate Presentation August 2023

2 This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements concerning the success and timing of planned regulatory filings and approvals, pre-commercial activities, commercialization strategy and timelines, business strategy, product labels, cash runway, scalability, future clinical trials in presbyopia (P), dim light/night vision disturbance (DLD) and diabetic retinopathy (DR) / diabetic macular edema (DME), including the potential for Nyxol to be a “best in class” presbyopia drop, and timing of planned future clinical trials for APX3330, APX2009 and APX2014, timing and occurrence of an End-of-Phase 2 meeting with the FDA, the potential of a Phase 3 registration path for APX3330, the success and timing of planned regulatory filings, business strategy, cash runway, scalability, the potential for APX3330 to be the most advanced and the first line of therapy for DR patients, and the potential market opportunity for the slowing of DR progression. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success, costs, and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; (ii) regulatory requirements or developments; (iii) changes to clinical trial designs and regulatory pathways; (iv) changes in capital resource requirements; (v) risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vi) legislative, regulatory, political and economic developments, (vii) changes in market opportunities, (viii) risks that the partnership with Viatris may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates; (ix) the success and timing of commercialization of any of Ocuphire’s product candidates, including the scalability of Ocuphire’s product candidates and (x) the maintenance of Ocuphire’s intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and may be filed by the Company from time to time with the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. The Company makes no representation or warranty, express or implied, as to the accuracy or completeness of the information contained in or incorporated by reference into this presentation. Nothing contained in or incorporated by reference into this presentation is, or shall be relied upon as, a promise or representation by the Company as to the past or future. The Company assumes no responsibility for the accuracy or completeness of any such information. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. Disclosures and Forward-Looking Statements

3 Corporate Highlights Strong Financial Position to Advance APX3330 Late-Stage Clinical Candidates for Retinal Diseases Represent Multi-Billion Dollar Opportunity APX3330: Paradigm Changing, Non-invasive, Safe Oral Tablet for millions of NPDR patients that are currently left untreated Ref-1, a novel, dual target (angiogenesis and inflammation) for retinal diseases ZETA-1 Phase 2 demonstrated slowing progression of Diabetic Retinopathy (DR) with statistically significant efficacy on potential Phase 3 registration endpoint Nyxol: Eyedrops for refractive disorders Global License Agreement with Viatris to Fund all Development and Commercialization for Nyxol Indications: Reversal of Mydriasis (RM)- PDUFA Date on September 28, 2023. Approval would trigger $10M milestone Presbyopia- currently in Phase 3 Dim Light Disturbances- currently in Phase 3

4 Ocuphire Pipeline Product Candidate Indication Pre-clinical Phase 1 Phase 2 Phase 3 Regulatory Approval Upcoming Milestones APX3330 Oral Pill Diabetic Retinopathy (DR) EOP2 Meeting EOP2 Mtg Q4 2023 APX3330 Local Delivery Retina Select retinal drug delivery technology APX2009 and APX2014 Local Delivery Retina Select retinal drug delivery technology Nyxol® Eyedrops Reversal of Mydriasis (RM) Partnered with Viatris PDUFA Date Sep 28, 2023 Presbyopia (P) VEGA-2 Phase 3 Topline Data Q4 2023 Dim Light or Night Vision Disturbances (DLD) LYNX-2 2nd Phase 3 trial (n=150+)

5 Diabetic Retinopathy Market and Unmet Need

6 Diabetic Eye Disease is Common Cause of Blindness Diabetes and Diabetic Retinopathy (DR) https://webeye.ophth.uiowa.edu/eyeforum/tutorials/diabetic-retinopathy-med-students/Classification.htm https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011 https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193 Diabetes Mellitus is a group of diseases characterized by high blood glucose levels. Diabetes results from defects in the body's ability to produce and/or use insulin Diabetic retinopathy (DR) occurs when fluctuations or instability in blood glucose levels damages blood vessels in the retina Type 1 diabetes (T1D): The body produces very little or no insulin, which means that patients need daily insulin injections to maintain blood glucose levels Type 2 diabetes (T2D): The most common form of diabetes - either the body does not produce enough insulin, or resists insulin Normal Retina Diabetic Retina Two Types of DR Non-Proliferative Diabetic Retinopathy (NPDR) – most common form of DR – early stages of edema and exudates, blurred central vision Proliferative Diabetic Retinopathy (PDR) – later stage of DR, marked by abnormal blood vessels and scar tissue on retina Diabetic Macular Edema (DME) can occur at any stage of DR

7 American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions; Das UN. DME, retinopathy and age-related macular degeneration as inflammatory conditions. Arch Med Sci. 2016;12(5):1142-1157. doi:10.5114/aoms.2016.61918 Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 Guidehouse Triangulation of Global Data, Market Scope and Investor Forecasts (2020) AMD = Age-Related Macular Degeneration; DME = Diabetic Macular Edema ; BRVO = Branch Retinal Vein Occlusion National Center for Chronic Disease Prevention & Health Promotion. Health & economic costs of chronic diseases. Atlanta (GA): Centers for Disease Control & Prevention, US Department of Health and Human Services; 2018 Four-Year Visual Outcomes in a Randomized Trial of Intravitreous Aflibercept for Prevention of Vision Threatening Complications of Diabetic Retinopathy (Protocol W).” JAMA. February 7, 2023 Diabetic Retinopathy At a Glance Current Treatment Landscape Demonstrates Need for Non Invasive Therapies The number of people with DR expected to increase more than 14M by 2050 There are ~8M adults in the U.S. with NPDR DR is the leading cause of blindness among working- age adults with the median age of onset at 45 – 50 years Majority of moderate to severe patients with DR are not treated with anti-VEGF due to injection burden and no benefit to visual acuity Prevention of Progression is favored by payors in chronic disease such as diabetes which is the leading cost driver Physicians have no non-invasive options for NPDR with current standard being wait-and-monitor

8 American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions; Spherix Global Insights Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 Estimates are provided by the National Eye Institute, FactSheet, Global Data, and Research and Markets. Estimated values are rounded. Estimated prevalence in the U.S.; DME- Diabetic Macular Edema; Age-related Macular Degeneration; Geographic Atrophy; Retinal Vein Occlusion U.S Diabetic Retinopathy Market 10M Diabetic Retinopathy (DR) 8M NPDR Patients US Market Opportunity Target Patient Population ~$6B+ 27% 27% 24% 22% Proliferative diabetic retinopathy (PDR) Severe non-proliferative diabetic retinopathy (NPDR) Moderate non-proliferative diabetic retinopathy (NPDR) Mild non-proliferative diabetic retinopathy (NPDR) 78% NPDR Non-Proliferative DR Proliferative DR Majority of the DR patients are NPDR Severity  Target Population for APX3330 Real-World Chart Review of DR Patients in US % of Patients 34 Million Diabetics in US Types of DR

9 Spherix Global Insights: DR Market DYNAMIX October 2022 Early treatment diabetic retinopathy study research group. ophthalmology. 1991;98(5 suppl):823-33. Diabetes control and complications trial research group. N Engl J Med. 1993;329(14):997-86. Fathy C, Patel S, Sternberg P Jr, Kohanim S. Disparities in adherence to screening guidelines for diabetic retinopathy in the United States: a comprehensive review and guide for future directions. Semin Ophthalmol. 2016;31(4):364–377. doi: 10.3109/08820538.2016.1154170 Progression Based on DR Severity NPDR Patients are Rarely Treated with anti-VEGF Intravitreal Injections; Non-Invasive, Early Intervention is an Unmet Need 0% 20% 40% 60% 80% 100% Mild NPDR (35) Moderate NPDR (43) Moderately Severe NPDR (47) Severe NPDR (53) 5% 12% 26% 52% 14% 30% 48% 71% 25% 40% 66% 80% 1 Year Follow-up 5 Year Follow-up 3 Year Follow-up Percentage of Eyes that Worsen to PDR Regardless of severity, all eyes worsen over time

10 10% 20% 30% 40% 50% 60% 70% International US 59.5% 60.5% 17.0% 24.9% 7.7% 7.8% 4.9% 3.1% 10.9% 3.7% ASRS 2021 Preferences and Trends (PAT) Survey ASRS PAT Survey: Majority of Physicians Use a “Wait and Monitor” Approach for DR NPDR Patients Are Not Treated Proactively and Anti-VEGF Use is Limited How do physicians treat patients with severe NPDR without DME? Closely monitor retinopathy and encourage systemic glycemic control Consider anti-VEGF in some patients with poor glycemic control and/or other risks Consider anti-VEGF in some patients with good glycemic control and compliance Consider anti-VEGF therapy in all or most patients Other 0%

11 Diabetic Retinopathy Treatment Landscape

12 Landscape of Non-Invasive Therapies for Diabetic Retinopathy Ocuphire’s APX3330 is the Most Advanced and The Only Dual Mechanism Oral Drug Candidate Company websites and www.clinicaltrials.gov (as of July 31, 2023) ✓ Completed ◌ Ongoing ✕ Discontinued Company Drug Target/MOA Indication Route of Administration Phase 1 Phase 2 Phase 3 Primary Endpoint/ Secondary Endpoints APX3330 Ref-1 inhibitor (Anti-VEGF and Anti-inflammatory) DR Oral ✓ ✓ 2022 2020: 2-step DRSS @wk24 RG7774 CB2 receptor (cannabinoid) DR Oral ✓ ◌ 2020: 2-step DRSS @wk36 BAY1101042 Guanylate Cyclase activator DR Oral ✓ ◌ 2021: 2-step DRSS @wk24 OPL-0401 ROCK 1/2 inhibitor DR Oral ✓ ◌ 2021: 2-step DRSS @wk24 OTT166 Integrin inhibitor DR Eyedrop ✓ ◌ 2022: 2-step DRSS @wk24 Note: Two Tyrosine Kinase and a Plasma Kallikrein Inhibitors failed as orals in Phase 2 due to dose limiting adverse events (e.g., liver and cardiovascular) APX3330 Differentiation Mechanism: Dual MOA targeting validated retinal pathways of angiogenesis and inflammation Human exposure: >10,000 subject days of systemic exposure in humans at 600mg/day dose Favorable safety and tolerability

13 Landscape of Invasive Therapies (IVT/Suprachoroidal) for Diabetic Retinopathy Eylea®/Lucentis® Approved, But Not Used in Patients with NPDR; Rarely Used in Mild PDR Company Drug Target/MOA Route of Administration Phase 1 Phase 2 Phase 3 Commercial Eylea® (aflibercept) VEGF-A/B; PIGF Intravitreal ✓ ✓ ✓ *1 Lucentis® (ranibizumab) VEGF-A Intravitreal ✓ ✓ ✓ *2 KSI-301 (Tarcocimab) VEGF Intravitreal ✓ N/A ◌ EYP-1901 Voloronib* (TKI) Intravitreal ✓ ◌ BI 764524 Anti-Sema3A Ischemia modulator Intravitreal ✓ ◌ OTX-TKI Axitinib* (TKI) Intravitreal ✓ ◌ RGX-314 AAV8-VEGF Suprachoroidal (Gene Therapy) ✓ ✓ Completed ◌ Ongoing X Discontinued *Trials to Support Approval 1 Panorama Clinical Trial 2 Protocol I & T and Rise & Ride * Failed as oral/systemic treatments in retina due to dose limiting toxicity Company websites and www.clinicaltrials.gov (as of July 31, 2023) Eylea® is trademark of Regeneron and Lucentis® is trademark of Genentech

14 APX3330 Background

15 Logsdon et al (2018), Li et al (2014). APX3330 History and Ref-1 Inhibition Mechanism Ref-1 Involved in Key Pathways that Contribute to Diabetic Retinopathy and DME Mechanism of Action – Ref-1 Inhibition Hypoxia Ref-1 HIF-1α VEGF (Signaling Cascade) Inflammation Ref-1 NF-κB Other Growth Factors (Signaling Cascade) TNF-α Chemokines Neovascularization Lucentis® EYLEA® Anti-VEGF Steroids APX3330 Ref-1 (reduction-oxidation effector factor-1), a novel target for retinal diseases, is a transcription factor regulator of angiogenesis (VEGF) and inflammation (NFkB) Unique dual MOA decreases abnormal angiogenesis and inflammation Anti-VEGF injections do not target inflammation Previously developed by Eisai for hepatic inflammatory indications and by Apexian for solid tumors in 11 Phase 1 and 2 trials Extensively studied in over 20 in-vitro and animal studies with favorable efficacy and safety

16 APX3330: Drug Development History and Patents Significant Preclinical & Clinical Data Supporting Human Safety, MOA, and PK 12* Phase 1 & Phase 2 Trials Exposure in Humans >10,000 Subject Days at 600mg/day Patents to 2034+ Studied in inflammation/hepatitis & cancer patients (Studied by Eisai & Apexian, respectively) APX3330 New Chemical Entity Preclinical Efficacy & Toxicology Package APX3330 IND 6 Phase 1 Trials 5 Phase 2 Trials Phase 2 Trials Phase 3 Registration NDA Filing Focus on Ophthalmology * Includes ZETA-1 trial

17 Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018 Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID: 21378315 Fehrenbacher, J. C., Guo, C., Kelley, M. R. & Vasko, M. R. DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA repair function of APE1. Neuroscience 366, 23-35, doi:10.1016/j.neuroscience.2017.09.039 (2017). In-vitro Validation of Mechanism of Action APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection APX3330 reduces pro-inflammatory cytokines in LPS stimulated macrophages Increasing APX3330 dose VEGF APX3330 reduces VEGF protein expression in preclinical stroke model Control APX3330 APX3330 enhances Ref-1 endonuclease activity in dorsal root ganglion neurons APX3330 increases DNA oxidative repair and neuronal protection

18 APX3330 VEGF Effects in Normal Cells Abnormal Conditions (e.g., hypoxic): Increased level of VEGF activity Normal Conditions: Physiological level of VEGF activity Kamba 2007; Girardi 2010; Li 2014 APX3330 Investigator Brochure Biologic anti-VEGF agents inactivate VEGF directly and reduce VEGF levels below normal levels Inhibition of Ref-1 by APX3330 returns VEGF levels to normal levels VEGF is a growth factor that is necessary for normal function of multiple cell types including vascular endothelium and neurons  By returning VEGF levels to normal, APX3330 can reduce neovascularization, vascular leakage and the inflammatory response without adverse systemic effects The safety profile of APX3330 to date has not shown any of the adverse effects that has been seen with systemic administration of anti-VEGF biologics such as cardiovascular pathology, hypertension, arteriothrombotic events, or renal dysfunction APX3330 ARPE-19 cell line APX3330 prevents VEGF overproduction in ARPE-19 cells APX3330 Restores Normal Levels Unlike Biologic Anti-VEGFs that Reduce VEGF Below Normal

19 APX3330 ZETA-1 Clinical Trial

20 ZETA-1: Phase 2 Trial of Oral AP3330 in Subjects With Diabetic Retinopathy Multi-center, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial Primary: % subjects with ≥ 2 step improvement on DRSS (Diabetic Retinopathy Severity Scale1) at week 24 Secondary: DRSS improvement ≥1, ≥2, ≥3, ≥4 study eye, fellow eye, binocular DRSS worsening ≥1, ≥2, ≥3, ≥4, study eye, fellow eye, binocular Progression to vision threatening complications Central subfield thickness (CST) Best Corrected Distance Visual Acuity (BCDVA) DME fellow eye status Safety and tolerability Exploratory: Inflammatory cytokines Endpoints 25 US sites N = 103 participants with moderately severe to severe NPDR or mild PDR (DRSS 47, 53, 61) Key inclusion: ≥ 18 years of age DRSS 47, 53, or 61 Noncentral DME permitted2 ETDRS BCVA ≥ 60 letters (20/63) Key exclusion: OCT CST >320 µm2 Center involved DME allowed in fellow eye Anti-VEGF within past 6 months3 HbA1c ≥ 12.0% Eligibility Criteria 103 subjects enrolled (FPFV Apr 2021 to LPLV Aug 2022) Topline announced in January 2023 1:1 By Central Reading Center Center-Involved DME in Fellow Eye is Acceptable Includes Systemic or IVT VEGF www.clinicaltrials.gov (NCT04692688); Eylea® is registered trademark of Regeneron NPDR = non-proliferative diabetic retinopathy PDR = proliferative diabetic retinopathy Week 0 Week 12 Week 24 Week 4 Primary Endpoint APX3330 600mg/day (BID) Placebo BID Randomization

21 ZETA-1: Baseline Demographics and Systemic Characteristics Well-Balanced Across Arms ZETA-1 Clinical Trial APX3330 n=51 Placebo n=52 Age (years) mean (range) 54.3 58.3 (26-81) (24-78) Sex: Male n (%) 24 (47%) 26 (50%) Race: White n (%) 40 (78%) 41 (79%) Ethnicity: Hispanic or Latino n (%) 28 (55%) 23 (44%) Diabetes Status (years) mean (range) 15 (0-36) 16 (0-58) Systolic Blood Pressure (mmHg) mean 136 139 Diastolic Blood Pressure (mmHg) mean 82 80 Heart Rate (beats/min) mean 77 76 Hemoglobin A1C (%) mean 8.4 8.3 Body Mass Index (kg/m^2) mean 31 31 DRSS Scores APX3330 n=51 Placebo n=52 Total n=103 BCVA Study Eye Letters (mean) 81 78 80 (20/25 Snellen) BCVA Fellow Eye Letters (mean) 76 77 77 (20/32 Snellen) OCT CST Study Eye (µm) 270 271 271 OCT CST Fellow Eye (µm) 292 286 289 Intraretinal Fluid in the Center of SE Y – 21 N – 26 Y – 12 N – 31 Y – 33 N – 57 Intraretinal Fluid at the Foveal Cente r of SE Y – 1 N – 20 Y – 1 N – 11 Y – 2 N – 31 Intraocular Pressure in Study Eye (mmHg) 15 16 15 APX3330 n=49 Placebo n=52 DRSS Score – Study Eye 47 (Moderately severe to severe NPDR) 22 (43%) 18 (35%) 53 (Moderately severe to severe NPDR) 25 (49%) 28 (54%) 61 (Mild proliferative diabetic retinopathy) 4 (8%) 6 (12%) DRSS Score – Fellow Eye 43 or Lower (Mild to moderate NDPR or better) 15 (31%) 13 (25%) 47 (Moderately severe to severe NPDR) 15 (31%) 20 (38%) 53 (Moderately severe to severe NPDR) 12 (25%) 10 (19%) 61 (Mild proliferative diabetic retinopathy) 1 (2%) 4 (8%) 65 or Higher (Moderate to severe prolif. DR) 6 (12%) 5 (10%) Demographics Key Visual Metrics Good Visual Acuity Fluid Below 320µm Note: 15 fellow eyes were CST>320 microns (center-involved DME eyes)

22 Percent of Subjects With ≥ 2-Step Improvement in DRSS From Baseline ZETA-1 Did Not Meet the Week 24 Phase 2 Primary Endpoint (based on Anti-VEGF Precedence for DR) 30% 25% 20% 15% 10% 5% 0% 35% Percent of Subjects (%) (N=49) (N=46) p=0.98 p=0.27 4% 7% 8% n=41 n=39 0% n=48 n=47 Week 12 Visit Week 24 Placebo (N=50) APX3330 (N=48) ZETA-1 Clinical Trial Note: Large “N” indicates total number of participants within each arm for the mITT population. Small “n” indicates total number of evaluable eyes for each respective endpoint and arm. Percent of Subjects With ≥ 2-step Improvement in DRSS From Baseline by Visit (mITT) – Study Eye

23 Clinically Meaningful Registration Endpoints in DR Systemic Drugs Should Evaluate DRSS Change in Both Eyes; To Be Formally Confirmed at EOP2 FDA Meeting 10 81-85 71-75 Local Drugs (Intravitreal Injections) Systemic Drugs Precedent approvable endpoint for locally- delivered drugs (Non-Systemic) in DR: ≥ 2-step DRSS improvement in study eye Aflibercept (PANORAMA trial) Ranibizumab (RISE/RIDE/DRCR trials) Potential approvable endpoints for systemic drug in DR (to be confirmed at the EOP2 FDA meeting) include: ≥ 3-step binocular DRSS improvement ≥ 3-step binocular DRSS worsening End-of-Phase 2 meeting with FDA to align on binocular ≥ 3-step DRSS worsening (i.e., sum of right and left eye change in DRSS) as an acceptable primary endpoint for registration This endpoint is distinct from historical anti-VEGF IVT precedent due to different delivery Source: ZETA-1 Clinical trial 1. Nair P, Aiello LP, Gardner TW, Jampol LM, Ferris FL III. Report From the NEI/FDA Diabetic Retinopathy Clinical Trial Design and Endpoints Workshop. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5127-5142. doi: 10.1167/iovs.16-20356. PMID: 27699406; PMCID: PMC6016432. FDA accepts improvement OR worsening (prevention of progression)1 of the disease AND DRSS is an established surrogate endpoint for DR

24 8% 16% 18% 32% 20% 6% 0% 0% 11% 36% 36% 34% 34% 28% 17% 11% 9% 0% 5% 10% 15% 20% 25% 30% 35% ≥ 4 Steps Worsening ≥ 3 Steps Worsening ≥ 2 Steps Worsening ≥ 1 Steps Worsening No Change ≥ 1 Step ≥ 2 Step ≥ 3 Step ≥ 4 Step Improvement Improvement Improvement Improvement Percent of Subjects (%) Placebo (n=50) APX3330 (n=47) DRSS Worsening DRSS Improvement Percent of Subjects with Binocular Improvement or Worsening in DRSS at Wk 24 APX3330 Demonstrated Statistical Efficacy on the Pre-Specified, Planned Phase 3 Registration Endpoint Percent of Subjects With Binocular Improvement or Worsening in DRSS of ≥ 1, ≥ 2, ≥ 3, and ≥ 4 Steps From Baseline (mITT-LOCF) 40% ZETA-1 Clinical Trial; p values shown if p<0.20 Table 14.2.2.7, March 2023 p<0.05 p=0.18 2%

25 Change in DRSS Score by Patient by Eyes 0% Patients in APX3330 Treatment Group had Binocular 3-Step Worsening DRSS Bar Legend Green: Both Eyes Improving Blue: 1 Eye Improving and 1 Eye Unchanged Purple: 1 Eye Improving and 1 Eye Worsening Orange: no change OU Gray: 1 Eye Worsening and 1 Eye Unchanged Red: Both Eyes Worsening Patients (n=47) Patients (n=47) -3 3 Presented on 8/1/23 at ASRS

26 Change in DRSS Score by Patient by Eyes 16% Patients in Placebo Treatment Group had Binocular 3-Step Worsening Patients (n=50) DRSS Bar Legend Green: Both Eyes Improving Blue: 1 Eye Improving and 1 Eye Unchanged Purple: 1 Eye Improving and 1 Eye Worsening Orange: no change OU Gray: 1 Eye Worsening and 1 Eye Unchanged Red: Both Eyes Worsening -3 3 Presented on 8/1/23 at ASRS

27 % of Subjects With Binocular ≥ 3-Step Worsening in DRSS and Progression to PDR APX3330 Prevented Progression of Structural Retinal Abnormalities 16% 0% 0% 0% 5% 10% 15% 20% Percent of Subjects (%) Visit Placebo (N=49) APX3330 (N=46) Week 12 n=50 n=47 12% p=0.07 Percent of Subjects With Worsening in DRSS of ≥3 Steps From Baseline by Visit Binocular Eyes (mITT-LOCF) It is estimated ~25% of untreated patients may progress by ≥ 3 steps in binocular DRSS over 1 year1 ZETA-1 Clinical Trial 1 Sun JK, Evidence for DR Progression and Regression from Clinical Trials. Presented at NDI/FDA DR Clinical Trials Design and Endpoints Workshop, June 26, 2015. 24% 14% 0 5 10 15 20 25 30 Placebo (n=49) (n-48) Subjects Developing PDR (%) (n=48) (n=50) APX 3330 Treatment Group p=0.22 Percentage of Subjects Developing PDR (mITT Population) at week 24 APX3330 reduced the percentage of subjects who developed PDR over the course of 24 weeks Week 24 n=50 n=47 19% 5% 0% 5% 10% 15% 20% 25% % of Subjects Placebo (n=43) APX3330 (n=40) Treatment Group p=0.07 Percentage of Subjects with ≥ 5 Letters of BCVA Lost at Week 24 (Safety Population) BCVA data shows fewer APX3330 treated subjects losing visual acuity compared to placebo at week 24 p=0.04

28 APX3330 SAEs: Dyskinesia, TIA, Chest pain Placebo SAEs: Vertigo, Asthenia, Multiple organ dysfunction, Bradycardia, CAD, Cholelithiasis, COVID-19 pneumonia, Cellulitis, Respiratory failure, Skin ulcer, Peripheral embolism AEs → Withdrawal APX3330: Presyncope, Dyspnea; Placebo: DME (both eyes) *Preferred Term within Organ Class ZETA-1: Treatment Emergent Adverse Events Oral APX3330 Showed a Favorable Safety and Tolerability Profile Consistent with Prior Trials Placebo (n=52) APX3330 (n=51) Total AEs 120 91 #of Subjects with AEs 35 (67%) 29 (57%) Treatment-related AEs 17 (14%) 14 (15%) Serious AEs 11 (9%) 3 (3%) Subjects Withdrawals Due to AEs 1 (2%) 2 (4%) Deaths 1 (2%) 0 (0%) AEs in >5% of Subjects* Diabetic Retinal Edema 5 (10%) 2 (4%) Diabetic Retinopathy 6 (12%) 1 (2%) Vitreous detachment 3 (6%) 0 (0%) Cataract 1 (2%) 3 (6%) Pruritus 1 (2%) 6 (12%) Rash 1 (2%) 3 (6%) COVID-19 5 (10%) 1 (2%) APX3330 Safety Profile: Limited AEs, most mild in severity Pruritis: Mild and resolved without APX3330 dose de-escalation or discontinuation AEs similar to or less than placebo Few serious treatment-related AEs, all unrelated to study medication No ocular AEs other than expected DR progression Lower incidence of clinical DR/DME worsening with APX3330 Patients continued routine medications to manage their diabetes comorbidities | Eye disorders |

29 APX3330 - Phase 2 Summary and Next Steps APX3330 demonstrated favorable safety and tolerability with compelling potential to slow progression of diabetic retinopathy ZETA-1 statistically significant results on potential Phase 3 registration endpoint: 0% APX3330-treated patients had a binocular ≥ 3-step worsening of DRSS from baseline compared with 16% for placebo-treated patients (p=0.04) ZETA-1 Summary Further analysis of ZETA-1 Phase 2 data, including insights for Phase 3 trial design Prepare for EOP2 FDA meeting in Q4 2023 to formally confirm Phase 3 design and registration endpoint Advance APX3330 into Phase 3 program with long-term exposure (up to 2 years) APX3330 Next Steps To have a clinically meaningful impact on preventing progression to reduce likelihood of vision loss in diabetic retinopathy patients Our Goal for Patients

DR is one of the largest markets in retina with 10M patients in US and over 100M worldwide Majority of the NPDR patients are not candidates for approved biologics treatments and are left untreated APX3330 first-in-class oral drug that inhibits Ref-1 which reduces VEGF and inflammatory cytokines to normal physiological levels Prevention of worsening is a clinically meaningful potential registration endpoint that was met in ZETA-1 study No subjects (0%) treated with APX3330 had a binocular ≥ 3-step DRSS worsening from baseline compared with 16% for placebo (p=0.04) after 24 weeks of treatment APX3330 demonstrated favorable safety & tolerability in diabetic patients An EOP2 meeting with FDA is confirmed in Q4 2023 APX3330 has the potential to be an early, non-invasive preventative treatment for the 8 million NPDR patients with the potential to treat other organs affected by diabetes (e.g., kidney disease, peripheral neuropathy) Broad prescriber base including general ophthalmology, optometry and primary care due to favorable safety 30 APX3330 Key Takeaways

31 Nyxol

32 Global Partnership with Viatris for Nyxol Viatris Has Selected Nyxol to be a Key Element of its Global Eye Care Division Fully funded development and commercialization costs for all 3 Nyxol indications Partner for Nyxol global commercialization Allows Ocuphire to focus on APX3330 development Strengthens cash position into 2025 $35 million upfront Funding for potentially all R&D and commercialization for all 3 indications globally $130 million in regulatory and sales milestones First potential $10 million milestone payment on FDA approval in RM Tiered double digit royalties through 2040

33 Reversal of Mydriasis (RM) P DLD Dim Light or Night Vision Disturbances (DLD) Presbyopia Nyxol as a Single Drop Nyxol with LDP Adjunctive Therapy 1 0.4% 2 RM R M NYXOL® EYE DROPS THREE INDICATIONS NEW PARTNERSHIP WITH VIATRIS

34 Summary of Nyxol Trial Results Comprehensive Body of Clinical Data Supporting Efficacy and Safety Across 3 Indications Indication & Status Primary Endpoint Efficacy Data Key Secondary Endpoint(s) Safety & Tolerability RM PDUFA 9/28/23 Return to baseline pupil diameter at 90 minutes after dilation Met Phase 3 primary endpoint MIRA-3: 58% Nyxol vs. 6% placebo MIRA-2: 49% Nyxol vs. 7% placebo (p<0.0001) MIRA-4: 64% Nyxol vs. 25% placebo Efficacy across all mydriatic agents, iris color, 1 or 2 drops, and all ages (3-80) Presbyopia (Nyxol Alone) Phase 3 ≥3 line gain in near vision with loss of no more than 1 line in distance vision Met planned Phase 3 primary endpoint VEGA-1: 29% Nyxol vs.12% placebo at 12 hrs post-Nyxol dose (p=0.02) Durable near vision (18 hrs) Optimal pupil size Pupillary light reflex No headaches No blurry vision ~5% mild redness No change in IOP No SAEs Most AEs were mild Presbyopia (Nyxol + LDP) Phase 3 Met Phase 2 primary endpoint Met planned Phase 3 primary endpoint VEGA-1: 61% combo post-LDP dose (30 min) + post-Nyxol dose (12 hrs) vs. 14% placebo (p<0.0001) Durable near vision gain Optimal pupil size Pupillary light reflex DLD 2nd Phase 3 ≥3 lines (eye test) of improvement in mesopic low contrast best-corrected distance visual acuity (mLCVA) Met Phase 3 primary endpoint LYNX-1: 13% Nyxol vs. 3% placebo at Day 8 (p<0.05) and 21% in Nyxol vs.3% placebo at Day 15 (p<0.01) Improvement visual acuity measures (distance and near) in dim light conditions

35 Corporate Highlights Late-Stage Retinal Pipeline Represents Multi-Billion Dollar Opportunity in Unmet NPDR Patients APX Pipeline Driven by a Paradigm Changing, Dual Target Ref-1 Platform for Retinal Diseases Global License Agreement with Viatris to Fund Development and Commercialization of Nyxol for All Refractive Indications Strong Financial Position to Fund Operations into 2025 APX3330 – Novel, Non-Invasive, Safe Oral Tablet to Treat Diabetic Retinopathy

Restore Vision & Clarity www.ocuphire.com ir@ocuphire.com Ocuphire Pharma Appendix 36

37 Silva et al. ARVO 2021 Annual Meeting *Published data on EYLEA. This study was performed independently from APX3330 study and is a cross-study comparison. **Li 2014; *** Pasha 2018; ****Jiang 2011 (Vldlr -/- : Very Low-Density Lipoprotein receptor knock-out mice) Preclinical Data: Oral APX3330 Blocks Neovascularization Lesion Volume Decrease with Oral APX3330 in Murine Laser CNV Model Similar to EYLEA® Data L-CNV Mouse Retina Model Lesion Size and Corresponding Fluorescent Stains in L-CNV Models Treated with APX3330 at 25 mg/kg oral gavage APX3330 APX3330 Gavage OCT Vehicle 25 mg/kg 50 mg/kg Lesion Volume -55% Silva et al, 2021 L-CNV Mouse Retina Model *EYLEA Efficacy was also seen after single intravitreal injection of 20µM APX3330 in mouse L-CNV model** Efficacy was also seen after dosing intraperitoneal injection of 50 mg/kg twice daily, 5 days on/2 days off, for 2 weeks in mouse L-CNV model*** Efficacy was also seen after single intravitreal injection of 20µM APX3330 in Vldlr -/- mice model**** -44%

38 505(b)(2) Regulatory Pathway Supported by Prior Phentolamine Approvals in non-ophthalmic Indications Illustration for educational purposes Nyxol’s Differentiated MOA as an Alpha-1 Blocker No Engagement of Ciliary Muscle, No Headaches and Lower Risk of Retinal Detachment Phentolamine is the Active Ingredient in Nyxol: a non-selective α Antagonist Phentolamine blocks α1 receptors on the Iris Dilator Muscle up to 24 hours Decreases pupil size (moderately) without affecting the iris sphincter or ciliary muscles Allows for 3 indications: RM, Presbyopia and DLD

39 Phase 2 Phase 1 Ocuphire Nyxol + 0.4% pilo Visus Brimochol® (carbachol + brim) Other Cholinergic Agonists* Cholinergic Agonist* (pilocarpine) Lenz Aceclidine; Aceclidine + brim Eyenovia MicroLine (2% pilo) Alpha Antagonist & low dose pilocarpine* Alpha Antagonist NDA Allergan VUITYTM; (1.25% pilo) Orasis CSF-1 (Low dose pilo) Phase 3 Nyxol’s potential differentiation: New MOA class (iris dilator muscle inhibitor) Favorable safety and tolerability (e.g.: no headaches, no accommodative spasm, no risk of retinal detachment) 24-hour durability Broad range of patients including high myopes Improvement in night vision disturbances Nyxol+LDP may offer added efficacy and tunability Ocuphire Nyxol (0.75% phentolamine) Pupil modulation MOA Combination drugs Lens softening MOA X Novartis EV-006 Lens Softening * acts on sphincter and ciliary muscles in dose- dependent manner Corporate Websites as of July 31, 2023, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020 A New, Differentiated MOA and Combination Therapy Offers Tunability

40 Management Team with Decades of Drug Development Experience Drey Coleman VP, Clinical Operations Amy Rabourn, CPA SVP, Finance Charlie Hoffmann, MBA SVP, Corporate Development Mitch Brigell, PhD Head, Clinical Development and Strategy Daniela Oniciu, PhD Global Head, R&D, Chemistry and Product Development Ronil Patel, MTech, MS SVP, Operations and BD Chris Ernst Global Head, QA and Manufacturing Barbara Withers, PhD VP, Clinical and Regulatory Strategy Bindu Manne Head, Market Development and Commercialization Laura Gambino Director, Project Management Richard Rodgers, MBA Interim CEO

41 Ocuphire's World-Class Medical Advisory Board Chief Medical Advisor, Ocuphire Refractive Specialist Jay Pepose, MD, PhD UCLA School of Medicine Refractive Specialist Y. Ralph Chu, MD Northwestern University Refractive Specialist Zaina Al-Mohtaseb, MD Baylor College of Medicine Refractive Specialist James Katz, MD University of Illinois Refractive Specialist Marguerite McDonald, MD Columbia University Refractive Specialist Mitch Jackson, MD University of Chicago Refractive/ Glaucoma Specialist Thomas Samuelson, MD University of Minnesota Refractive/Glaucoma Specialist Inder Paul Singh, MD The Chicago Medical School Eliot Lazar, MD Georgetown University elCON Medical Retinal Specialist Peter Kaiser, MD Harvard Medical School Retinal Specialist David Lally, MD Vanderbilt University Retinal Specialist Michael Allingham, MD, PhD University of North Carolina Retinal Specialist David Boyer, MD Chicago Medical School Retinal Specialist David Brown, MD Baylor University Retinal Specialist Jeffrey Heier, MD Boston University Retinal Specialist Anat Lowenstein, MD, PhD The Hebrew University Retinal Specialist Caroline Baumal, MD University of Toronto Medical School Optometry Douglas Devries, OD University of Nevada Optometry Paul Karpecki, OD Indiana University Optometry Justin Schweitzer, OD Pacific University College of Optometry Optometry Selina McGee, OD Northeastern State University Optometry Leslie O’Dell, OD Salus University Co-Founder Apexian/APX3330 Mark Kelley, PhD Indiana University

42 Ocuphire Board of Directors Sean Ainsworth, MBA Lead Independent Director, Board Director Jay Pepose, MD, PhD Board Director Susan Benton, MBA Board Director Cam Gallagher, MBA Chair, Board Director James Manuso, PhD/MBA Board Director Richard Rodgers, MBA Interim President & CEO Board Director

Document and Entity Information	Aug. 01, 2023
Cover [Abstract]
Document Type	8-K
Amendment Flag	false
Document Period End Date	Aug. 01, 2023
Entity File Number	001-34079
Entity Registrant Name	Ocuphire Pharma, Inc.
Entity Central Index Key	0001228627
Entity Incorporation, State or Country Code	DE
Entity Tax Identification Number	11-3516358
Entity Address, Address Line One	37000 Grand River Avenue, Suite 120
Entity Address, City or Town	Farmington Hills
Entity Address, State or Province	MI
Entity Address, Postal Zip Code	48335
City Area Code	248
Local Phone Number	957-9024
Title of 12(b) Security	Common Stock, par value $0.0001 per share
Trading Symbol	OCUP
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	false
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false