#1January 25, 2023 ZETA-1 APX3330 Topline Results Investor Webcast Ocuphire Restore Vision & Clarity#22 Disclosures 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 future clinical trials for APX3330, 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 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) Nyxol partnership may not facilitate the commercialization or market acceptance of Ocuphire's product candidates; (x) the success and timing of commercialization of any of Ocuphire's product candidates, including the scalability of Ocuphire's product candidates and (xi) 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#33 Agenda and Speakers Topic ZETA-1 Key Takeaways and APX3330 Oral MOA ZETA-1 Trial Design and Demographics ZETA-1 Efficacy Findings ZETA-1 Safety Findings Overall Summary and Next Steps Q&A FREE Mina Sooch, MBA Founder and Chief Executive Officer Charles Wykoff, MD, PhD Vitreoretinal Specialist Mitch Brigell, PhD Head of Clinical Development and Strategy Mark Kelley, PhD APX Scientific Founder and Medical Advisor Ocuphire#44 Ocuphire PHARMA ZETA-1 Key Takeaways and APX3330 Oral MOA#5LO 5 ZETA-1 Trial: Key Takeaways APX3330 achieved statistical significance on a key pre-specified secondary endpoint of preventing clinically meaningful progression of diabetic retinopathy (as defined by binocular 3 or more steps worsening on the DRSS¹) after 24 weeks of treatment Trend toward more efficacy at 24 weeks vs 12 weeks, suggests that the 52-week Phase 3 trial may generate a larger signal due to an increase in % of placebo subjects who progress Prevention of 3-step worsening (binocular) is a suitable endpoint for an oral, systemically drug ➜ Ocuphire plans to go forward with this potential registration endpoint in Phase 3 following confirmation with the FDA in EOP2 meeting Oral APX3330 demonstrated favorable safety and tolerability Retinal KOLs feedback suggest that slowing of DR progression with an oral agent would be a useful treatment in patients with background DR and good visual function If approved, APX3330 could be an important new primary preventative therapeutic option that could be used in a large number of diabetic patients who are earlier in their disease 1. diabetic retinopathy severity score Source: ZETA-1 Clinical Trial Ocuphire#6CO 6 APX3330 History and Ref-1 Inhibition Mechanism Ref-1 Involved in Multiple Key Pathways that Contribute to Diabetic Retinopathy and DME Mechanism of Action - Ref-1 Inhibition Нурохіа ↓ Ref-1 HIF-1a VEGF (Signaling Cascade) Anti-VEGF Lucentis® EYLEAⓇ APX3330 — Neovascularization 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) is a novel target discovered by Dr. Mark R. Kelley at Indiana University School of Medicine and Ocuphire's Scientific Advisor for APX program ● APX3330 is a small molecule oral drug candidate and a first-in-class inhibitor of Ref-1 • APX3330 previously developed by Eisai for multiple hepatic inflammatory indications and later by Apexian for advanced solid tumors in 11 Phase 1 and 2 trials Similar oncology origin as approved anti-VEGFs ● MOA uniquely decreases both abnormal angiogenesis and inflammation by blocking pathways downstream of Ref-1 Extensively studied in over 20 in-vitro and animal studies with favorable efficacy and safety Ocuphire PHARMA#77 Ocuphire PHARMA ZETA-1 Trial Design and Demographics#88 DR/DME ZETA-1 Phase 2 Design Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar To Eylea P3 DR Trial) ZETA-1 25 US sites 90-100 participants with moderately severe-to-severe NPDR or mild PDR Noncentral DME is permitted in study eye and central DME allowed in fellow eye Eligibility Screening NPDR = non-proliferative diabetic retinopathy PDR = proliferative diabetic retinopathy 1:1 Randomization Week 0 APX3330 600mg/day (BID) Primary Endpoint NPDR = non-proliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy ZETA-1 Clinical Trial is Sponsored by Ocuphire Pharma Week 4 Week 12 Placebo BID 103 Subjects Enrolled (FPFV Apr 2021- LPLV Aug 2022) Top Line Announced in Early 2023 Week 24 Endpoints Primary: % subjects with ≥ 2 step improvement on DRSS (Diabetic Retinopathy Severity Scale) at wk 24 Secondary: ● DRSS worsening* DRSS improvement* Progression to vision threatening complications Central subfield thickness (CST) Best Corrected Distance Visual Acuity (BCDVA) Rescue subjects • DME fellow eye status Safety and tolerability Exploratory: Labs / PK *Potential Phase 3 approvable endpoints Ocuphire#99 CO Key Eligibility Criteria in ZETA-1 Oral Medication Provides Binocular Treatment; DME Allowed in Fellow Eye Inclusion ● ● ● Males or non-pregnant females ≥ 18 years of age At least one eye with DR DRSS 47, 53, or 61, confirmed by a central reading center) in which PRP and intravitreal injections of an anti-VEGF agent can be safely deferred for ≥ 6 months in the opinion of the Investigator BCVA assessed by ETDRS protocol letters score of ≥ 60 letters (Snellen equivalent 20/63 or better) in the study eye Body mass index (BMI) between 18 and 40 kg/m², inclusive Source: ZETA-1 Clinical trial Exclusion ● • Prior treatment in study eye with focal/grid laser photocoagulation within the past year, PRP at any time, systemic or intravitreal anti-VEGF agents within last 6 months in study eye ● ● Retinopathy from causes other than diabetes in study eye Presence of center involved diabetic macular edema (DME) defined as a central subfield thickness (CST) ≥ 320 µm on SD-OCT Center involved DME in the fellow eye is allowed ● Intraocular steroids including triamcinolone and dexamethasone implant within the last 6 months Fluocinolone implant within the last 3 years HbA1c ≥ 12.0% Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardio- vascular disorders) that might interfere as deemed by Investigator Ocuphire#1010 ZETA-1: Demographics Well-Balanced Across Arms Demographics Age (years): Mean (Range) Source: ZETA-1 Clinical Trial Sex: Male n (%) Female n (%) Race: White n (%) African American n (%) Asian n (%) Other n (%) Ethnicity: Hispanic or Latino n (%) Not Hispanic or Latino n (%) Time (Years) Since Onset of Diabetes: Mean APX3330 n=51 54.3 (26-81) 24 (47%) 27 (53%) 40 (78%) 5 (10%) 3 (6%) 3 (6%) 28 (55%) 23 (45%) 15 Placebo n=52 58.3 (24-78) 26 (50%) 26 (50%) 41 (79%) 6 (12%) 1 (2%) 0 (0%) 23 (44%) 29 (56%) 16 Total n=103 56.3 (24-81) 50 (49%) 53 (52%) 81 (79%) 11 (11%) 4 (4%) 3 (3%) 51 (50%) 52 (51%) 16 Ocuphire#1111 ZETA-1: Baseline DRSS Scores Study and Fellow Eye Well-Balanced Across Arms DRSS Score - Study Eye DRSS Category (Screening) Study Eye [n (%)] 47 (Moderately severe to severe NPDR) 53 (Moderately severe to severe NPDR) 61 (Mild proliferative diabetic retinopathy) DRSS Score - Fellow Eye DRSS Category (Screening) Fellow Eye [n (%)] 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) Source: ZETA-1 Clinical Trial APX3330 n=51 22 (43%) 25 (49%) 4 (8%) APX3330 n=45 14 (31%) 13 (29%) 12 (27%) 1 (2%) 5 (11%) Placebo n=52 18 (35%) 28 (54%) 6 (12%) Placebo n=49 12 (24%) 19 (39%) 9 (19%) 4 (8%) 5 (10%) Total n=103 40 (39%) 53 (52%) 10 (10%) Total n=94 26 (28%) 32 (34%) 21 (22%) 5 (5%) 10 (11%) Ocuphire#1212 ZETA-1: Baseline Characteristics Study and Fellow Eye Well-Balanced Across Arms Baseline Characteristic BCVA letters in Study Eye Letters Read (mean) BCVA letters in Fellow Eye Letters Read (mean) OCT Central Subfield Thickness in Study Eye (μm) OCT Central Subfield Thickness in Fellow Eye (μm) Intraocular Pressure in Study Eye (mmHg) 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) Note: Blood markers are normal range as baselines Source: ZETA-1 Clinical Trial APX3330 n=51 81 76 270 292 15 136 82 78 8.4 31 Placebo n=52 78 77 271 286 16 139 80 76 8.3 31 Total n=103 80 (20/25 Snellen) 77 (20/32 Snellen) 271 289 15 138 81 77 8.3 31 Good Visual Acuity Fluid Below DME Definition of 320 micron (μm) Ocuphire#1313 ZETA-1 Efficacy Findings Ocuphire PHARMA#14DRSS 10, 12 DR Absent Step Background on DRSS Assessment & Binocular DRSS 1 14 1 14, 15, 20 DR Questionable 2 2 35 Mild NPDR 3 3 Diabetic Retinopathy Severity Scale (DRSS) 43 Moderate NPDR 4 47 Moderately Severe NPDR 5 5 53 Severe NPDR 6 6 60, 61 Mild PDR 7 65 Moderate PDR 8 8 71-75 High-risk PDR 9 81-85 Advanced PDR Monocular calculation: Change in DRSS Step in a Single Eye (Study Eye or Fellow Eye) Binocular calculation: Composite Change in DRSS Step in Study Eye and Change in DRSS Step in Fellow Eye The ETDRS diabetic retinopathy severity scale (DRSS) is a categorical tool for clinical trials that contains 10 discreet steps from no retinopathy to severe proliferative retinopathy derived from the grading of fundus photographs for each eye at a central reading center. Each patients' study eye had a baseline DRSS step of 5, 6 or 7 to be included in this trial. 10 10 Ocuphire#15Percent of Subjects (%) 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) 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=47 p=0.27 4% n=46 Week 12 Visit Placebo (N=49) 8% n=40 p=0.93 8% n=39 Week 24 APX3330 (N=46) 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) - Qualified Fellow Eye 4% n=24 p=0.20 14% n=14 Week 12 Visit Placebo (N=49) 5% n=22 p=0.20 27% n=11 Week 24 ■APX3330 (N=46) Source: 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. Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting 15 Ocuphire#1616 Clinically Meaningful Registration Endpoints in DR Path Forward to Phase 3: Systemic Drugs Should Evaluate DRSS Change in Both Eyes In retina, opportunity for approval to show improvement OR worsening (prevention of progression)* Precedent approvable endpoint for locally delivered drugs (non-systemic) in DR: ≥ 2-step DRSS improvement in study eye Eylea (Panorama trial) Lucentis (Rise/Ride trials) ● ● Oral/systemic drugs are different than anti-VEFG IVT as they treat both eyes Therefore, a suitable evaluation is change in both eyes (binocular) 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 ZETA-1 Phase 2 trial for APX3330 evaluated key secondary endpoints ≥ 3-step binocular DRSS improvement and worsening to inform design of the Phase 3 registration trial *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. Ocuphire Source: ZETA-1 Clinical trial#1717 Percent of Subjects With Improv. or Worsening in Binocular DRSS of ≥ 3-Steps Potential Phase 3 Endpoints as an Oral Drug; Results Improve with Time Percent of Subjects (%) Percent of Subjects With Improvement or Worsening in DRSS of ≥ 3 Steps From Baseline Binocular Eyes (mITT-LOCF) - Week 12 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% 12% p=0.07 0% n=45 n=49 Subjects with >= 3 Steps Worsening (observed) Placebo (N=49) p=0.61 4% APX3330 (N=46) 7% n=49 n=45 Subjects with >= 3 Step Improvement (observed) Percent of Subjects (%) 18% 16% 14% 12% 10% 8% 6% 4% 2% 0% Percent of Subjects With Improvement or Worsening in DRSS of ≥ 3 Steps From Baseline Binocular Eyes (mITT-LOCF) - Week 24 16% p=0.04 p=0.38 6% APX3330 (N=46) 11% 0% n=49 n=45 n=49 n=45 Subjects with >= 3 Steps Worsening Subjects with >= 3 Step Improvement (observed) (observed) Placebo (N=49) Source: ZETA-1 Clinical Trial Note: Large "N" indicates total number of participants within each arm for the mITT-LOCF population. Small "n" indicates total number of evaluable eyes for each respective endpoint and arm. Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting Ocuphire#18Percent of Subjects (%) Percent of Subjects With Binocular Worsening in DRSS of ≥ 3-Step Selected Primary Registration Endpoint for Phase 3, To Be Formally Confirmed at EOP2 FDA Meeting 20% 15% 10% 5% 0% Percent of Subjects With Worsening in DRSS of 23 Steps From Baseline by Visit Binocular Eyes (MITT-LOCF) 12% n=49 p=0.07 Week 12 0% n=45 Visit Placebo (N=49) APX3330 (N=46) 16% n=49 p=0.04 Week 24 0% n=45 Based on extrapolation from ZETA-1, -25% of patients may progress by ≥ 3 steps in binocular DRSS over 1 year if untreated Source: ZETA-1 Clinical Trial Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting Note: Large "N" indicates total number of participants within each arm for the mITT-LOCF population. Small "n" indicates total number of evaluable eyes for each respective endpoint and arm: Predprire 18#1919 DRSS Letter Score CFB 6 Waterfall by Subject Binocular Change in DRSS at Week 24 8 Subjects in Placebo and 0 in APX3330 had a 3-Step DRSS Worsening at Week 24 5 1 0 Placebo Worsening in Binocular DRSS at Week 24 ≥ 3 Steps Worsening n=8 Subject (n=17) DRSS Letter Score CFB Source: ZETA-1 Clinical Trial Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting 6 + 3 0 APX3330 Worsening in Binocular DRSS at Week 24 Waterfall plots show subjects with worsening ≥ 3 Steps Worsening n=0 |||||| ▬▬▬▬▬▬ Subject (n=15) Ocuphire#20Patients, % 20 80 60 40 20 0 Historic Data for Diabetic Patients on DR Progression The Worse the DRSS, the Higher the Risk of Vision Threatening Complications 4.2 9.8 ≥3-Step Worsening Lucentis data shows that 28% untreated eyes will worsen DRSS by ≥ 2-steps over 1 year Stability of DR from Month 36 to month 48 Received Re-treatment During OLE (n=285) No Re-treatment During OLE (n=82) 5.3 18.3 2-Step Worsening 15.1 13.4 1-Step Worsening 66.3 54.9 Stable 6.7 2.4 1.1 1.2 1-Step 2-Step Improvement Improvement DRSS Change from Month 36 to Month 48 Source - Sun JK, Evidence for Diabetic Retinopathy Progression and Regression from Clinical Trials. Presented at NDI/FDA DR Clinical Trials Design and Endpoints Workshop, June 26, 2015. 1.4 0 23-Step Improvement Cumulative Incidence, % Probability of developing PDR or DME is greater with higher baseline NPDR severity 60- 40- 20- 15 Years Severe nonproliferative diabetic retinopathy (state 4) Moderate nonproliferative diabetic retinopathy (state 3) Mild nonproliferative diabetic retinopathy (state 2) No retinopathy (state 1) 5 10 20 Source - Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes. N Engl J Med. 2017 Apr 20;376(16):1507-1516. doi: 10.1056/NEJMoa1612836. PMID: 28423305; PMCID: PMC5557280 25 30 Ocuphire#2121 ZETA-1 Safety Findings Ocuphire PHARMA#2222 PK/Safety Data Findings Favorable Safety Data for Oral APX3330 APX3330 PK/serum levels as predicted at 600 mg/day Serum levels of APX3330 are consistent with previous findings in hepatitis and oncology trials Fewer subjects lost 5 or more letters at week 24 with APX3330 compared to placebo Limited treatment related AEs (mostly mild and transient) Only rash (6% APX3330 vs 2% placebo) and pruritus (12% APX3330 vs 2% placebo) were seen more frequently in APX3330 than placebo No treatment related serious TEAES • No effect on vital signs (BP, HR) No effect on physical exam No change in liver, kidney, or heart functions No effect on IOP No effect on clinical labs ● ● ● ● ● ● ● ZETA-1 Clinical Trial (Safety Population) Ocuphire#23Treatment Emergent Adverse Events APX3330 Safety Similar To or Better Than Placebo 103 Subjects Enrolled 91 Subjects completed thru week 24 211 Treatment Emergent AEs (64 Subjects) 91 (29 Subjects) APX3330, 120 (35 Subjects) Placebo 31 Treatment-Related AEs (in 21 Subjects) APX3330 14 AEs in 10 subjects (10 mild, 4 moderate, O severe) withdrew due to an AE 2 APX, 2 PBO Placebo 17 AEs in 11 subjects (8 mild, 9 moderate, 0 severe) 5 lost to follow-up 2 APX, 3 PBO 23 ZETA-1 Clinical Trial Safety Population (subject to final review) 3 withdrew consent or site closure 2 APX, 1 PBO 0 Treatment-Related AES involving liver, heart, kidney, brain, lung, or vital signs 14 SAEs (in 11 Subjects) 3 unrelated SAEs in APX3330 Oral APX3330 safety profile consistent with that seen in prior trials 11 unrelated SAES in Placebo Ocuphire#2424 Summary and Next Steps Ocuphire PHARMA#2525 APX3330 Product Candidate Profile for Multiple Retinal Indications Oral, First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data from 12 Completed Trials APX3330: Well-tolerated Oral Dose up to 600 mg/day | Twice Daily Dosing Favorable Safety Profile Over 350 Subjects (Healthy, Liver, Cancer, Diabetic) Treated Notably, Several Subjects Dosed ~1 Yr and Others 24-Wks MOA and Efficacy Signals in DR Novel MOA for Treating Retina ↓ Inflammation ↓ Abnormal Angiogenesis Daily vs. episodic exposure Good Patient Compliance in ZETA-1 with Convenient Oral Dosing APX3330 Demonstrated Slowing of Progression of Diabetic Retinopathy Few Systemic AEs Across All Doses (120mg-720mg) < 5% Mild Skin Rash (reversible) < 5% Mild Diarrhea No Treatment-Related Organ Toxicity (Liver, Cardiovascular {BP, HR}, Kidney, Neurologic, Pulmonary) Minimal Ocular Side Effects* Source: ZETA-1 Clinical Trial; *1 subject had vision blur thought to be related by investigator in ZETA-1 Ocuphire#26Broad Opportunities to Treat Retinal Diseases with APX Platform APX3330 May Treat Patients Across Retinal Diseases as Single Agent or Adjunctive Therapy Addressable Market Mild NPDR 6M US Market Opportunity 34 Million Diabetics in US 10M Diabetic Retinopathy Moderate to Severe NPDR (DRSS 43-53) 1M ~8M+ DR Patients ~$10B+ Market Revenues PDR (DRSS >60) 1M APX3330 APX3330 APX2009/APX2014/APX3330 (Local Delivery) + Anti-VEGF treatments Inflammatory component is common across these retina indications as well & potentially addressable by MOA of Ref-1 DME 1M Source: 1. American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions; 2. 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 3. Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 4. Estimates are provided by the National Eye Institute, FactSheet, Global Data, and Research and Markets. Estimated values are rounded. 26 5. Estimated prevalence in the U.S.; DME- Diabetic Macular Edema; Age-related Macular Degeneration; Geographic Atrophy; Retinal Vein Occlusion Wet AMD 2M Dry AMD 10M+ GA 1M Potential First Oral Rx for Retina Diseases with Multi-Billion Revenue Opportunity Ocuphire#2727 Landscape of Systemic Therapies for Diabetic Retinopathy Ocuphire's APX3330 is the Most Advanced Oral Drug Moving into EOP2 Mtg and Phase 3 Company Lilly aerpio pharmacei B BAYER E R Drug LY333531 ÇAKB-9778 Ocuphire APX3330 OALKAHESTⓇ AKST4290 Roche RG7774 Boehringer Ingelheim Valo OPL-0401 BAY1101042 Guanylate Cyclase activator Protein Kinase C inhibitor Tie2 www.clinicaltrials.gov Target/MOA Ref-1 inhibitor (Anti-VEGF and Anti-inflammatory) CCR3 Eotaxin inhibitor BI 1467335 AOC3 CB2 receptor (cannabinoid) ROCK 1/2 inhibitor Indication DR DR DR DR DR DR DR DR Route of Administration Oral Subcutaneous Oral Oral Oral Oral Oral Oral Phase 1 Phase 2 Phase 3 X 2006 ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ X 2019 ✓ X 2022 X 2021 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) Primary Endpoint/ Secondary Endpoints 2002: BCVA 3-line 2017: 2-step DRSS @wk24 2020: 2-step DRSS @wk24 2021: 2-step DRSS @wk24 2021: 2-step DRSS @wk24 2020: 2-step DRSS @wk36 2017: Primary:safety@wk12 Secondary: 2-step DRSS@wk12 2021: 2-step DRSS @wk24 Completed Ongoing X Discontinued Ocuphire FHPERS#2828 Efficacy Signal Intravitreal: Percent of patients with ≥ 2 step improvement on the DRSS score at week 24 and 52 compared to placebo in 2 well-controlled trials ● ● APX3330 has Potential to be Early Preventative Therapy for DR Patients Systemic: Percent of patients with ≥ 3-step worsening on binocular DRSS at week 24 and 52 compared to placebo in 2 well-controlled trials Safety Approval depends on a product's benefit outweighing its risks in the intended. population, this benefit should be evaluated in multi-center, 2-year clinical trials ● Non-Invasive Treatment Option FDA does not require comparative arm of approved anti-VEGF injections (Eylea) for DR Eylea® label; APX3330 Investigator Brochure, ZETA-1 clinical trial FDA Physician/ Patients Efficacy Signal Clinically meaningful decrease in diabetic retinopathy severity ● OR Safety ● Early intervention with oral may prevent progression of DR to vision loss ● No major organ toxicities Well-tolerated (e.g., AEs acceptable if mild and infrequent for oral) Non-Invasive Treatment Option Eylea®, although approved, is currently not used as standard of care because of the treatment burden for asymptomatic DR patients Ability to be prescribed by wide-range of healthcare providers (ophthalmologists, optometrists, endocrinologists, primary care, etc.) Oral option increases global access, especially in underserved regions Ocuphire#2929 Key Takeaways and Next Steps Key Takeaways • APX3330 is the most advanced oral program in development for diabetic eye disease • APX3330 demonstrated favorable safety with compelling potential to slow progression of diabetic retinopathy • ZETA-1 statistically significant results on 'binocular 3-step worsening DRSS' endpoint provides a potential Phase 3 registration endpoint Goal Next Steps Further analysis of ZETA-1 Phase 2 data, including insights for Phase 3 registration trial design Plan for the EOP2 FDA meeting for APX3330 in DR indication Data presentations at medical meetings Advance APX3330 development (CGMP drug, NDA-enabling work, first Phase 3 trial, regional partnerships) → fully funded into 2025 To have a clinically meaningful impact on preventing progression to reduce likelihood of vision loss in diabetic retinopathy patients Ocuphire#30Ocuphire Pharma Nasdaq: OCUP Upcoming Catalysts: ✓ Topline Results APX3330 ZETA-1 P2b trial for DR/DME (Early 2023) EOP2 FDA Meeting for APX3330 (2H 2023) Pivotal Phase 3 Trials for Nyxol in Presbyopia with 1st Data Readouts (Late 2023) Potential Approval of 1st Nyxol NDA (Late 2023) Stock Price¹ Market Cap¹ Cash (Pro-Forma)2,3 Shares Outstanding² Average Daily Volume Cash Runway Into 2025 $3.67 $77M -$49 M 20.8M ~200k Shares ¹ As of close on January 24, 2023; 2 End of 3Q22 (10-Q); 3 Includes upfront payment from License Agreement Corporate Highlights Two Lead Clinical-Stage Novel Drugs Addressing Multiple Large Ophthalmology Markets (~$20B US total) with Limited to No Competition & Patent Coverage to 2034+ APX3330 oral tablets Diabetic Retinopathy/Diabetic Macular Edema (DR/DME) - diabetic eye disease Nyxol preservative-free eyedrops Reversal of Mydriasis (RM) - eye dilation Presbyopia (P) - age-related blurry near vision Night Vision Disturbances (NVD) – halos, glares, starbursts Successful Execution of 5 Trials in Last 2 Years with 6 Positive Phase 3 & Phase 2 Data Read-outs for Nyxol in RM, Presbyopia, and NVD NDA submitted Nov 2022 for Nyxol's first indication in RM Global License Agreement Signed in Late 2022 with Viatris to Develop and Commercialize Nyxol for All Indications in the US and Globally Strong Financial Position (with No Debt) to Support Operations into 2025 and Coverage from 5 Biotech Research Analysts Ocuphire PHARMA#31Ocuphire Restore Vision & Clarity www.ocuphire.com [email protected] in Ocuphire Pharma Thank You and Q&A