#1August 2023 Ocuphire Corporate Presentation Ocuphire Restore Vision & Clarity#2Disclosures and Forward-Looking Statements 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. Ocuphire 2#3Corporate Highlights 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 Ocuphire ● Strong Financial Position to Advance APX3330 PHARMA ● 3#4Ocuphire Pipeline Product Candidate APX3330 Oral Pill APX3330 Local Delivery APX2009 and APX2014 Local Delivery NyxolⓇ Eyedrops Ocuphire Indication Diabetic Retinopathy (DR) Retina Retina Reversal of Mydriasis (RM) Presbyopia (P) Dim Light or Night Vision Disturbances (DLD) Pre-clinical Phase 1 Phase 2 Phase 3 EOP2 Meeting Regulatory Approval Partnered with Viatris Upcoming Milestones I EOP2 Mtg Q4 2023 Select retinal drug delivery technology Select retinal drug delivery technology PDUFA Date Sep 28, 2023 VEGA-2 Phase 3 Topline Data Q4 2023 OLYNX-2 2nd Phase 3 trial (n=150+) 4#55 Ocuphire PHARMA Diabetic Retinopathy Market and Unmet Need#6Diabetic Eye Disease is Common Cause of Blindness Diabetes and Diabetic Retinopathy (DR) 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 FE S Ocuphire 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 - 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 Diabetic retinopathy (DR) occurs when fluctuations or instability in blood glucose levels damages blood vessels in the retina 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 CO#7Diabetic Retinopathy At a Glance Current Treatment Landscape Demonstrates Need for Non Invasive Therapies ^^^^^^^ MM There are ~8M adults in the U.S. with NPDR Ocuphire PHARMA The number of people with DR expected to increase more than 14M by 2050 22 Physicians have no non-invasive options for NPDR with current standard being wait-and-monitor ta Prevention of Progression is favored by payors in chronic disease such as diabetes which is the leading cost driver 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 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 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 7#8U.S Diabetic Retinopathy Market Majority of the DR patients are NPDR Severity →Target Population for APX3330 Types of DR Target Patient Population Ocuphire 34 Million Diabetics in US 10M Diabetic Retinopathy (DR) Non-Proliferative DR US Market Opportunity Proliferative DR 8M NPDR Patients ~$6B+ 78% NPDR Real-World Chart Review of DR Patients in US % of Patients 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 22% 24% 27% 27% Proliferative diabetic retinopathy (PDR) Severe non-proliferative diabetic retinopathy (NPDR) Moderate non-proliferative diabetic retinopathy (NPDR) Mild non-proliferative diabetic retinopathy (NPDR) 8#9Progression Based on DR Severity NPDR Patients are Rarely Treated with anti-VEGF Intravitreal Injections; Non-Invasive, Early Intervention is an Unmet Need Ocuphire Percentage of Eyes that Worsen to PDR 100% 80% 60% 40% 20% 0% Regardless of severity, all eyes worsen over time 5% 14% 25% 12% 30% Mild NPDR (35) Moderate NPDR (43) 40% 26% 48% 66% Moderately Severe NPDR (47) 52% 71% 80% Severe NPDR (53) 5 Year Follow-up 3 Year Follow-up 1 Year Follow-up 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 9#10ASRS 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 Ocuphire 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 ASRS 2021 Preferences and Trends (PAT) Survey Other 0% 4.9% 3.1% 7.7% 7.8% 10% International 10.9% 3.7% US 20% 17.0% 24.9% 30% 40% 50% 59.5% 60.5% 60% 70% 10#1111 Ocuphire PHARMA Diabetic Retinopathy Treatment Landscape#12Landscape of Non-Invasive Therapies for Diabetic Retinopathy Ocuphire's APX3330 is the Most Advanced and The Only Dual Mechanism Oral Drug Candidate Company Ocuphire Roche PHARMA BAYER BAYER Valo Ocuphire OCUTERRA THERAPEUTICS Drug APX3330 RG7774 Target/MOA Ref-1 inhibitor (Anti-VEGF and Anti-inflammatory) CB2 receptor (cannabinoid) BAY1101042 Guanylate Cyclase activator OPL-0401 ROCK 1/2 inhibitor OTT 166 Integrin inhibitor Indication DR DR DR DR DR Route of Administration Oral Oral Company websites and www.clinical trials.gov (as of July 31, 2023) Oral Oral Eyedrop Phase 1 Phase 2 Phase 3 ✓ 2022 ✓ ✓ ✓ ✓ ✓ Primary Endpoint/ Secondary Endpoints 2020: 2-step DRSS @wk24 2020: 2-step DRSS @wk36 2021: 2-step DRSS @wk24 2021: 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) Completed Ongoing 2022: 2-step DRSS @wk24 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 X Discontinued 12#13Landscape of Invasive Therapies (IVT/Suprachoroidal) for Diabetic Retinopathy EyleaⓇ/Lucentis® Approved, But Not Used in Patients with NPDR; Rarely Used in Mild PDR Company REGENERON Roche KODIAK EYEPOINT PHARMACEUTICALS Boehringer Ingelheim Therapeutix REGENXBIO® Drug Eylea (aflibercept) Lucentis® (ranibizumab) KSI-301 (Tarcocimab) EYP-1901 BI 764524 OTX-TKI RGX-314 Target/MOA VEGF-A/B; PIGF VEGF-A VEGF Voloronib* (TKI) Anti-Sema3A Ischemia modulator Axitinib* (TKI) AAV8-VEGF Ocuphire Company websites and www.clinical trials.gov (as of July 31, 2023) Route of Administration Eylea® is trademark of Regeneron and Lucentis® is trademark of Genentech Intravitreal Intravitreal Intravitreal Intravitreal Intravitreal Intravitreal * Failed as oral/systemic treatments in retina due to dose limiting toxicity Suprachoroidal (Gene Therapy) Phase 1 ✓ ✓ Phase 2 ✓ N/A Completed Phase 3 Commercial ✓*1 ✓*2 Ongoing X Discontinued *Trials to Support Approval 1 Panorama Clinical Trial 2 Protocol I & T and Rise & Ride 13#1414 APX3330 Background Ocuphire PHARMA#15APX3330 History and Ref-1 Inhibition Mechanism Ref-1 Involved in Key Pathways that Contribute to Diabetic Retinopathy and DME Ocuphire Mechanism of Action - Ref-1 Inhibition PHARMA Hypoxia ↓ Ref-1 HIF-1a Anti-VEGF VEGF (Signaling Cascade) LucentisⓇ EYLEAⓇ APX3330 — Neovascularization (H Logsdon et al (2018), Li et al (2014). Inflammation Ref-1 NF-kB TNF-a Chemokines Other Growth Factors (Signaling Cascade) Steroids ● • 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 15#16APX3330: Drug Development History and Patents Significant Preclinical & Clinical Data Supporting Human Safety, MOA, and PK APX3330 New Chemical Entity Ocuphire Preclinical Efficacy & Toxicology Package * Includes ZETA-1 trial 12* Phase 1 & Phase 2 Trials APX3330 IND 6 Phase 1 Trials Exposure in Humans >10,000 Subject Days at 600mg/day 5 Phase 2 Trials Studied in inflammation/hepatitis & cancer patients (Studied by Eisai & Apexian, respectively) Phase 2 Trials Patents to 2034+ Phase 3 Registration Focus on Ophthalmology NDA Filing 16#17VEGF In-vitro Validation of Mechanism of Action APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection APX3330 reduces VEGF protein expression in preclinical stroke model Control VEGF % Positive area (+SE) 2.6 1.3 0.0 Ocuphire 0.1mm VEGF T1DM-MCAO APX3330 *p<0.05 n=7/group * +APX3330 APX3330 reduces pro-inflammatory cytokines in LPS stimulated macrophages TNF-α 14000 12000 10000 8000 μg/mL 6000 4000 2000 0 APX3330 LPS (1 µg/mL) 14000 12000 10000 8000 6000 4000 2000 0 APX3330 LPS (1 µg/mL) 0 ug/mL 0 ug/mL 0 ug/mL + 6.3 ug/mL 12.5 ug/mL 25 ug/mL IL-6 h 0 ug/mL 6.3 ug/mL 12.5 ug/mL + + + 25 ug/mL + Increasing APX3330 dose % increase in APE1 repair activity APX3330 increases DNA oxidative repair and neuronal protection 120 115 110 105 100 95 N=4 0 *1 12.5 25 APX3330 (μM) * 50 APX3330 enhances Ref-1 endonuclease activity in dorsal root ganglion neurons 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). 17#18APX3330 VEGF Effects in Normal Cells APX3330 Restores Normal Levels Unlike Biologic Anti-VEGFs that Reduce VEGF Below Normal Normal Conditions: Physiological level of VEGF activity Abnormal Conditions (e.g., hypoxic): Ocuphire Increased level of VEGF activity PHARMA Biologic anti-VEGF agents inactivate VEGF directly and reduce VEGF levels below normal levels Biologic Anti-VEGF Treatment Kamba 2007; Girardi 2010; Li 2014 APX3330 Investigator Brochure APX3330 Anti-Ref-1 Treatment Inhibition of Ref-1 by APX3330 returns VEGF levels to normal levels APX3330 prevents VEGF overproduction in ARPE-19 cells VEGF Concentrations (% of Control) 500 450 400 350 300 250 200 150 100 50 0 OXLDL APX3330 ARPE-19 cell line + * 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 p<0.05 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 + 150μg/mL + 30μM 18#1919 APX3330 ZETA-1 Clinical Trial Ocuphire PHARMA#20• 25 US sites ● ZETA-1: Phase 2 Trial of Oral AP3330 in Subjects With Diabetic Retinopathy Multi-center, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial ● ● Key inclusion: ● Eligibility Criteria . N = 103 participants with moderately severe to severe NPDR or mild PDR (DRSS 47, 53, 61) ● Key exclusion: ≥ 18 years of age DRSS 47, 53, or 61 Noncentral DME permitted² ETDRS BCVA ≥ 60 letters (20/63) OCT CST >320 μm² Center involved DME allowed in fellow eye Anti-VEGF within past 6 months³ HbA1c ≥ 12.0% Ocuphire PHARMA By Central Reading Center Center-Involved DME in Fellow Eye is Acceptable 1. 2. 3. Includes Systemic or IVT VEGF Randomization 1:1 APX3330 600mg/day (BID) Week 0 www.clinicaltrials.gov (NCT04692688); Eylea® is registered trademark of Regeneron NPDR = non-proliferative diabetic retinopathy PDR = proliferative diabetic retinopathy Week 4 Week 12 Placebo BID Primary Endpoint Week 24 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 ● ● ● ● Endpoints ● 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 103 subjects enrolled (FPFV Apr 2021 to LPLV Aug 2022) Topline announced in January 2023 20#21ZETA-1: Baseline Demographics and Systemic Characteristics Well-Balanced Across Arms Demographics Age (years) mean (range) Sex: Male n (%) Race: White n (%) Ethnicity: Hispanic or Latino n (%) Diabetes Status (years) mean (range) Systolic Blood Pressure (mmHg) mean Diastolic Blood Pressure (mmHg) mean Heart Rate (beats/min) mean Hemoglobin A1C (%) mean Body Mass Index (kg/m^2) mean Ocuphire APX3330 n=51 54.3 (26-81) 24 (47%) 40 (78%) 28 (55%) 15 (0-36) 136 82 77 8.4 31 Placebo n=52 ZETA-1 Clinical Trial 58.3 (24-78) 26 (50%) 41 (79%) 23 (44%) 16 (0-58) 139 80 76 8.3 31 DRSS Scores APX3330 n=49 DRSS Score - Study Eye 47 (Moderately severe to severe NPDR) 53 (Moderately severe to severe NPDR) 61 (Mild proliferative diabetic retinopathy) DRSS Score - Fellow Eye 43 or Lower (Mild to moderate NDPR or better) 47 (Moderately severe to severe NPDR) 53 (Moderately severe to severe NPDR) 61 (Mild proliferative diabetic retinopathy) 65 or Higher (Moderate to severe prolif. DR) 22 (43%) 25 (49%) 4 (8%) 15 (31%) 15 (31%) 12 (25%) 1 (2%) 6 (12%) Placebo n=52 18 (35%) 28 (54%) 6 (12%) 13 (25%) 20 (38%) 10 (19%) 4 (8%) 5 (10%) Note: 15 fellow eyes were CST>320 microns (center-involved DME eyes) Key Visual Metrics APX3330 n=51 Placebo n=52 BCVA Study Eye Letters (mean) BCVA Fellow Eye Letters (mean) OCT CST Study Eye (μm) OCT CST Fellow Eye (um) Intraretinal Fluid in the Center of SE Intraretinal Fluid at the Foveal Cente r of SE Intraocular Pressure in Study Eye (mmHg) 81 76 270 292 Y - 21 N - 26 Y-1 N - 20 15 78 77 271 286 Y - 12 N - 31 Y-1 N-11 16 Total n=103 80 (20/25 Snellen) 77 (20/32 Snellen) 271 289 Y - 33 N - 57 Y-2 N - 31 15 21 Good Visual Acuity Fluid Below 320μm#22Percent 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) Ocuphire Percent of Subjects (%) 35% 30% 25% 20% 15% 10% 5% 0% Percent of Subjects With ≥ 2-step Improvement in DRSS From Baseline by Visit (mITT) - Study Eye 0% n=48 p=0.27 4% n=47 Week 12 Visit ■Placebo (N=50) 7% n=41 p=0.98 8% ■APX3330 (N=48) n=39 Week 24 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. 22#23Clinically Meaningful Registration Endpoints in DR Systemic Drugs Should Evaluate DRSS Change in Both Eyes; To Be Formally Confirmed at EOP2 FDA Meeting Ocuphire 10, 12 DR Absent 14, 15, 20 DR Questionable 35 Mild NPDR ● 43 ● Moderate NPDR Precedent approvable endpoint for locally- delivered drugs (Non-Systemic) in DR: 47 Moderately Severe NPDR Local Drugs (Intravitreal Injections) ≥ 2-step DRSS improvement in study eye Aflibercept (PANORAMA trial) Ranibizumab (RISE/RIDE/DRCR trials) FDA accepts improvement OR worsening (prevention of progression)¹ of the disease AND DRSS is an established surrogate endpoint for DR 53 Severe NPDR 60, 61 Mild PDR 65 71-75 Moderate PDR High-risk PDR ● Systemic Drugs Potential approvable endpoints for systemic drug in DR (to be confirmed at the EOP2 FDA meeting) include: 81-85 Advanced PDR ≥ 3-step binocular DRSS improvement ≥ 3-step binocular DRSS worsening This endpoint is distinct from historical anti-VEGF IVT precedent due to different delivery 10 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 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. 23#24Percent 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) Percent of Subjects (%) 40% 35% €30% 25% 20% 15% 10% 5% 0% Ocuphire 8% 0% DRSS Worsening p<0.05 16% 0% > 4 Steps ≥ 3 Steps Worsening Worsening ZETA-1 Clinical Trial; p values shown if p<0.20 Table 14.2.2.7, March 2023 18% 11% 36% 34% ≥ 2 Steps ≥ 1 Steps Worsening Worsening Placebo (n=50) 36% 34% No Change 32% 28% DRSS Improvement APX3330 (n=47) 20% 17% 6% 11% p=0.18 2% 9% ≥ 2 Step ≥ 3 Step ≥ 4 Step ≥ 1 Step Improvement Improvement Improvement Improvement 24#25Change in DRSS Score by Patient by Eyes 0% Patients in APX3330 Treatment Group had Binocular 3-Step Worsening Improvement Change in DRSS Worsening -6 -2,-2 -4 -2,-2 -1,-3 -3 -2 2 3 4 -3,-2 6 0,-3 -1,-1 -1,-1 -1,-1 APX3330 Binocular Change from Baseline @ Week 24 (MITT LOCF) -1,0 0,-1 -1,0-1,0 0,-1 Presented on 8/1/23 at ASRS 0,0 0,0 0,0 0,0 0,0 0,0 0,0 0,00 0,00 0,0 0,0 0,0 ¹,1 1,1 -1,1 Patients (n=47) 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 ▬▬▬▬▬▬▬▬▬▬ 1,0 1,0 0,1 0,1 2,-1 -1,2 1,0 1,0 1,0 0,1 0,1 2,-1 IIII 0,2 1,1 1,1 0,2 1,1#26Change in DRSS Score by Patient by Eyes 16% Patients in Placebo Treatment Group had Binocular 3-Step Worsening Improvement Worsening Change in DRSS -6 -4 -3 Ń 2 3 -2,-2 -0,-3 -2,-1 -1,-1 -1,-1 -1,-1 0,-2 0₂-2 Presented on 8/1/23 at ASRS Placebo Binocular Change from Baseline @Week 24 (MITT LOCF) -1,0 -1,0 -1,0 0,-1 -1,0 -1,0 | | | | | | 0,0 0,0 0,0 0,0 0,0 0,0 0,0 0,0 0,0 Patients (n=50) 3,-3 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 -0,1 0,1 0,1 1,0 0,1 0,1 0,1 2,-1 0,2 3,0 0,3 3,0 -2,5 0,4 1,3 2,2 2,4 26#27% of Subjects With Binocular ≥ 3-Step Worsening in DRSS and Progression to PDR APX3330 Prevented Progression of Structural Retinal Abnormalities Percent of Subjects With Worsening in DRSS of 23 Steps From Baseline by Visit Binocular Eyes (mITT-LOCF) 20% ■Placebo APX3330 15% 12% p=0.07 10% D 5% 0% 0% Week 12 n=50 n=47 Ocuphire Visit ● 16% p=0.04 0% It is estimated ~25% of untreated patients may progress by ≥ 3 steps in binocular DRSS over 1 year¹ Week 24 n=50 n=47 30 25 20 15 10 Percentage of Subjects Developing PDR (mITT Population) at week 24 24% p=0.22 14% Placebo (n=50) APX 3330 (n=48) Treatment Group APX3330 reduced the percentage of subjects who developed PDR over the course of 24 weeks 25% 20% 15% 10% 5% 0% Percentage of Subjects with ≥ 5 Letters of BCVA Lost at Week 24 (Safety Population) 19% p=0.07 Placebo (n=43) APX3330 (n=40) Treatment Group 5% 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. BCVA data shows fewer APX3330 treated subjects losing visual acuity compared to placebo at week 24 27#28ZETA-1: Treatment Emergent Adverse Events Oral APX3330 Showed a Favorable Safety and Tolerability Profile Consistent with Prior Trials | Eye disorders | Total AEs Ocuphire PHARMA #of Subjects with AEs Treatment-related AEs Serious AEs Subjects Withdrawals Due to AEs Deaths AES in >5% of Subjects* Diabetic Retinal Edema Diabetic Retinopathy Vitreous detachment Cataract Pruritus Rash COVID-19 Placebo (n=52) 120 35 (67%) 17 (14%) 11 (9%) 1 (2%) 1 (2%) 5 (10%) 6 (12%) 3 (6%) 1 (2%) 1 (2%) 1 (2%) 5 (10%) APX3330 (n=51) 91 29 (57%) 14 (15%) 3 (3%) 2 (4%) 0 (0%) 2 (4%) 1 (2%) 0 (0%) 3 (6%) 6 (12%) 3 (6%) 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 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 28#29APX3330 - Phase 2 Summary and Next Steps ● ZETA-1 Summary Ocuphire 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) Our Goal for Patients APX3330 Next Steps 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) To have a clinically meaningful impact on preventing progression to reduce likelihood of vision loss in diabetic retinopathy patients 29, 29#30APX3330 Key Takeaways 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 Ocuphire PHARMA 30#3131 Nyxol Ocuphire PHARMA#32Global Partnership with Viatris for Nyxol Viatris Has Selected Nyxol to be a Key Element of its Global Eye Care Division Ocuphire Partner for Nyxol global commercialization Fully funded development and commercialization costs for all 3 Nyxol indications 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 32#33NYXOLⓇ EYE DROPS THREE INDICATIONS NEW PARTNERSHIP WITH VIATRIS TTT7 STZ VIATRIS™ RM P DLD Reversal of Mydriasis (RM) Presbyopia 1 Nyxol as a Single Drop 2 Pop SE HA 0.4% Nyxol with LDP Adjunctive Therapy L Dim Light or Night Vision Disturbances (DLD) 33#34Summary of Nyxol Trial Results Comprehensive Body of Clinical Data Supporting Efficacy and Safety Across 3 Indications Indication & Status RM PDUFA 9/28/23 Presbyopia (Nyxol Alone) Phase 3 Presbyopia (Nyxol + LDP) Phase 3 DLD 2nd Phase 3 Ocuphire Primary Endpoint Return to baseline pupil diameter at 90 minutes after dilation ≥3 line gain in near vision with loss of no more than 1 line in distance vision 23 lines (eye test) of improvement in mesopic low contrast best-corrected distance visual acuity (mLCVA) Efficacy Data 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 Met planned Phase 3 primary endpoint VEGA-1: 29% Nyxol vs. 12% placebo at 12 hrs post-Nyxol dose (p=0.02) 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) 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) Key Secondary Endpoint(s) Efficacy across all mydriatic agents, iris color, 1 or 2 drops, and all ages (3-80) Durable near vision (18 hrs) Optimal pupil size Pupillary light reflex Durable near vision gain Optimal pupil size Pupillary light reflex Improvement visual acuity measures (distance and near) in dim light conditions Safety & Tolerability No headaches No blurry vision ~5% mild redness No change in IOP No SAEs Most AEs were mild 34#35Corporate Highlights Late-Stage Retinal Pipeline Represents Multi-Billion Dollar Opportunity in Unmet NPDR Patients APX3330 - Novel, Non-Invasive, Safe Oral Tablet to Treat Diabetic Retinopathy 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 co Strong Financial Position to Fund Operations into 2025 Ocuphire PHARMA 35#36Appendix Ocuphire Restore Vision & Clarity www.ocuphire.com [email protected] in Ocuphire Pharma 36#37Preclinical 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 Vehicle Silva et al, 2021 Ocuphire 25 mg/kg 50 mg/kg Lesion Volume (µm³) APX3330 Gavage OCT Lesion Volume 8x106- 6x106 4x106- 2x106- 0 **** *** -55%. Vehicle 25 50 [APX3330] (mg/kg) (a) Day 7 (c) 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) Day 14 ONL L-CNV Mouse Retina Model *EYLEA Anti-VEGF164 Vehicle CNV lesion volume (μm³) 1.2x107- 9.0x106- 6.0x106- 3.0x106- 0.0- ✓ 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% Vehicle Anti-VEGF164 37#38Nyxol's Differentiated MOA as an Alpha-1 Blocker No Engagement of Ciliary Muscle, No Headaches and Lower Risk of Retinal Detachment Ocuphire PHARMA Phentolamine is the Active Ingredient in Nyxol: a non-selective a Antagonist DILATOR MUSCLE SPHINCTER MUSCLE SPHINCTER MUSCLE Illustration for educational purposes CILIARY MUSCLE Phentolamine blocks a1 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 505(b)(2) Regulatory Pathway Supported by Prior Phentolamine Approvals in non-ophthalmic Indications 38#39A New, Differentiated MOA and Combination Therapy Offers Tunability Nyxol's potential differentiation: 1) New MOA class (iris dilator muscle inhibitor) 2) Favorable safety and tolerability (e.g.: no headaches, no accommodative spasm, no risk of retinal detachment) 3) 24-hour durability 4) Broad range of patients including high myopes 5) Improvement in night vision disturbances ➤ Nyxol+LDP may offer added efficacy and tunability Ocuphire PHARMA Other Cholinergic Agonists* Alpha Antagonist Alpha Antagonist & low dose pilocarpine* Ocuphire Nyxol (0.75% phentolamine) Visus BrimocholⓇ (carbachol + brim) Ocuphire Nyxol + 0.4% pilo Lens Softening Corporate Websites as of July 31, 2023, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020 X Novartis EV-006 Lenz Aceclidine; Aceclidine + brim NDA Allergan VUITYTM; (1.25% pilo) Orasis CSF-1 (Low dose pilo) Phase 3 Phase 2 Eyenovia MicroLine (2% pilo) Phase 1 * Pupil modulation MOA Combination drugs Lens softening MOA acts on sphincter and ciliary muscles in dose- dependent manner Cholinergic Agonist* (pilocarpine) 39#40Management Team with Decades of Drug Development Experience MGI. PHARMA Richard Rodgers, MBA Interim CEO CARLSON SCHOOL OF MANAGEMENT UNIVERSITY OF MINNESOTA TESARO™ Abraxis BioScience SIRION Therapeutics Bindu Manne Head, Market Development and Commercialization Takeda UNC Shire PEMBROKE ThromboGenics® III MERCK Ocular equinox Therapeutix FLORIDA TECH BETALIO Revitalid POINT GUARD PARTNERS LLC Drey Coleman VP, Clinical Operations OCULOS Integrated Insight. Ronil Patel, MTech, MS SVP, Operations and BD UCF aerpio OCULOS Integrated Insight. Chris Ernst Global Head, QA and Manufacturing NORTHERN KENTUCKY Akebia THERAPEUTICS MEDPACE Charlie Hoffmann, MBA SVP, Corporate Development Tuck School of Business IIIII at Dartmouth TOOO Prudential Syber Goldman DevEx Sachs Ocularis Pharma Mitch Brigell, PhD Head, Clinical Development and Strategy KANSAS STATE aerpio & NOVARTIS UNIVERSITY Pfizer aerpio Laura Gambino Director, Project Management EASTERN MICHIGAN UNIVERSITY THERAPEUTICS GE aerpio SUBC Pfizer MIMICHIGAN ROSS Pfizer Barbara Withers, PhD VP, Clinical and Regulatory Strategy Amy Rabourn, CPA SVP, Finance Therapeutics NeuroBo PHARMACEUTICALS WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE Pfizer pwc Daniela Oniciu, PhD Global Head, R&D, Chemistry and Product Development UNIVERSITY of UF Gemphire Cerenis™ Pfizer THERAPEUTICS ESPERION® 40#41Ocuphire's World-Class Medical Advisory Board WHITSETT VISION GROUP Refractive Specialist Zaina Al-Mohtaseb, MD Baylor College of Medicine Chu Vision INSTITUTE Refractive Specialist Y. Ralph Chu, MD Northwestern University Jacksoneye Chief Medical Advisor, Ocuphire Refractive Specialist Jay Pepose, MD, PhD UCLA School of Medicine Refractive Specialist Mitch Jackson, MD University of Chicago MINNESOTA EYE CONSULTANTS PeposeVision INSTITUTE Refractive/ Glaucoma Specialist Thomas Samuelson, MD University of Minnesota the Midwest Center for Sight Refractive Specialist James Katz, MD University of Illinois OCLI Refractive Specialist Marguerite McDonald, MD Columbia University elCON Medical Refractive Specialist Eliot Lazar, MD Georgetown University The Eye Centers of Racine & Kenosha Refractive/Glaucoma Specialist Inder Paul Singh, MD The Chicago Medical School Duke Eye Center Retinal Specialist Michael Allingham, MD, PhD University of North Carolina > New England Eye Center Retinal Specialist INDIANA UNIVERSITY MERKEN BREK SENON CANCER CENTO Co-Founder Apexian/APX3330 Mark Kelley, PhD Indiana University Caroline Baumal, MD University of Toronto Medical School Retina-Vitreous Associates Medical Group Retinal Specialist David Boyer, MD Chicago Medical School TEL AVIV SOURASKY MEDICAL CENTER ICHILOV Retinal Specialist Anat Lowenstein, MD, PhD The Hebrew University OPHTHALMIC CONSULTANTS OF BOSTON EXCELLENCE Retinal Specialist Jeffrey Heier, MD Boston University Cleveland Clinic Retinal Specialist Peter Kaiser, MD Harvard Medical School RETINA COMUTANTS OF AMERICA Retinal Specialist David Brown, MD Baylor University NEW ENGLAND RETINA CONSULTANTS Retinal Specialist David Lally, MD Vanderbilt University KENTUCKY EYE INSTITUTE Optometry Paul Karpecki, OD Indiana University EYE CARE ASSOCIATES OF NEVADA Optometry Douglas Devries, OD University of Nevada MOA Optometry Leslie O'Dell, OD Salus University PHOIC BeSpoke Vision Optometry Selina McGee, OD Northeastern State University VANCE THOMPSON VISION Optometry Justin Schweitzer, OD Pacific University College of Optometry 41#42Ocuphire Board of Directors Cam Gallagher, MBA Chair, Board Director Ocuphire University of San Diego VELOSBIO ONCTERNAL therapeutics zentalis RetroSense THERAPEUTICS Richard Rodgers, MBA Interim President & CEO Board Director CARLSON SCHOOL OF MANAGEMENT UNIVERSITY OF MINNESOTA TESARO™ MGI. PHARMA Abraxis BioScience James Manuso, PhD/MBA Board Director 4 Columbia Business School astex™ pharmaceuticals Talfinium Investments, Inc. GALENICA BESTE FISTICHE TECNOLONT Sean Ainsworth, MBA Lead Independent Director, Board Director Washington University in St. Louis OLIN BUSINESS SCHOOL Allergan RetroSense THERAPEUTICS IMMUSOFT Programming Cures Théa let's open our eyes Susan Benton, MBA Board Director USF MUMA COLLEGE OF BUSINESS UNIVERRITY OF SOUBBLOKER BAUSCH+ LOMB Shire BOARD Jay Pepose, MD, PhD Board Director 5 UCLA PeposeVision INSTITUTE Wilmer Eye Institute David Geffen School of Medicine Washington University in St.Louis 42