#1Ocuphire Restore Vision & Clarity Ocuphire Pharma Investor R&D Day January 31, 2022#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 regulatory timelines, commercial timelines, cash runway, and future clinical trials in RM, presbyopia, NVD and DR/DME, including the potential for Nyxol to be a "best in class" presbyopia drop. 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 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) the effects of COVID-19 on clinical programs and business operations, (ix) the success and timing of commercialization of any 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 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 PHARMA IS HOSTING A VIRTUAL INVESTOR R&D DAY 1 MONDAY, JANUARY 31ST, 2022 10:00AM - 12:00PM EST www.ocuphire.com Ocuphire OCUP NasdaqListed Nasdaq PHARMA#3Ocuphire Investor R&D Day 1/31/22 Agenda & Speakers Agenda INDIANA UNIVERSITY MELVIN AND BEEN SIMON CANCER CENTER Mark Kelley, PhD 3 Paul Karpecki, OD KENTUCKY EYE INSTITUTE Speakers Ocuphire Mina Sooch, MBA President & CEO and Founder Jay Pepose, MD, PhD Peter Kaiser, MD Cleveland Clinic Cole Eye Institute Jacksoneye seeing beyond your imagination Mitchell Jackson, MD PeposeVision INSTITUTE David Boyer, MD Retina-Vitreous Associates Medical Group Bindu Manne Ocuphire Head of Commercialization James Katz, MD the Midwest Center for Sight Introductions & Company Overview I 10:00 am - 10:10 am Closing Remarks 12:10 pm - 12:15 pm I. APX3330 DR/DME Program ☆☆ II. Nyxol Reversal of Mydriasis Program III. Nyxol Presbyopia Program New Data ** New Data Time (EST) Corey Davis, LifeSci Advisors will moderate Q&A 10:10 am - 10:50 am 10:50 am 11:30 am - 11:30 am - 12:10pm Ocuphire PHARMA#44 Company Overview Presenter: Mina Sooch, CEO, Founder of Ocuphire Pharma Ocuphire Mina Sooch M.B.A Harvard University ● ● Ocuphire ● PHARMA Over 25 years of pharmaceutical and biotech experience as CEO, entrepreneur, venture capitalist and strategy consultant Successful track record of hundreds of millions of capital raise and leading private/public biotech companies Experience across multiple diseases (cardiovascular, oncology, renal, NASH, CNS, etc.) prior to ophthalmology Recipient of numerous awards including Deal Makers of the Year in 2016 and Alumni Commencement Speaker WSU College of Engineering in 2021#5LO 5 Ocuphire Pharma Restoring Vision and Clarity for Your Eyes, Today and Tomorrow Innovation Mira Execution Performance Vega Disruption Lynx Zeta Ocuphire PHARMA#6April 2021 Alcon Ophthalmology - An Attractive Biotech Sector Demographics, M&A, Regulatory Approvals and Efficient Trials Favor Ophthalmic Drugs Deal Activity SIMBRINZA $355M October 2021 Théa 6 THE CURACLE ~$2B December 2021 NOVARTIS GYROSCOPE VISION FOR LIFE ~$1.5B September 2021 REGENXBIO Allergan. an AbbVie company $1.75B December 2021 ▲Rayner ~$1B OMIDRIA December 2021 Genentech A Member of the Roche Group $670M LINEAGE CELL THERAPEUTICS Active M&A Aging Population Lower Cost, Quick Enrolling, Short Duration Clinical Trials Favorable Regulatory Environment New Product Approvals 7 of 60 Total FDA Drug Approvals in 2021 Were Ophthalmic Drugs¹ and 1 in 2022 Therapeutix™ Dextenza *SNDA (dexamethasone ophthalmic insert) 0.4mg for intracanalicular use Roche SuSvimo ranibizumab injection For Ocular Implant 100 Roche VABYSMO faricimab-svoa injection 6 mg Source:1.Endpoint Dec 29, 2021- Hitting a new record on drug approvals, the FDA offers a thumbs-up to another atopic dermatitis contender; OIS Year in Review 2021; Company press releases OYSTER POINT PHARMA Odp Santen Verkazia 1 mg/mL Allergan. an AbbVie company Vuity. BAUSCH- Health XIPERE (triamcinolone acetonide injectable suspension) 40 mg/mL Ovut SAMSUNG BIOEPIS BYOOVIZ™ Ranibizumab biosimilar Ocuphire PHARMA#79 Phase 1, Phase 2, and Phase 3 Trials 7 Nyxol & APX3330: Drug Development History and Patents Significant Preclinical & Clinical Data Supporting Human Safety, MOA, Efficacy, and PK Refractivel Retina P >330 Subjects Dosed Presbyopia NyxolⓇ Novel a1/ a2 Blocker 505(b)(2) Source: Eisai and Apexian Data Exposure in Humans 28 Days Night Vision Disturbances Reversal of Mydriasis Patent Coverage 2034+ NVD RM 11 Phase 1 & Phase 2 Trials DR APX3330 Oral REF-1 Inhibitor New Chemical Entity >340 Subjects Dosed Exposure in Humans 365 Days Patents to 2034+ Diabetic Retinopathy Diabetic Macular Edema DME Ocuphire PHARMA#88 Ocuphire Pipeline & Clinical Milestones Multiple Phase 3 & Phase 2 Clinical Data Readouts Anticipated Over the Next Year Product Candidate 0.75% NyxolⓇ Eye Drop 0.75% NyxolⓇ+ Low-Dose 0.4% Pilocarpine Eye Drops 0.75% NyxolⓇ Eye Drop APX3330 Oral Pill Indication APX2009 (Intravitreal or Reversal of Mydriasis (RM) Presbyopia (P) Dim Light or Night Vision Disturbances (NVD) Diabetic Retinopathy (DR)/ Macular Edema (DME) DME or Wet Age- Related Macular Local Delivery) Degeneration (wAMD) Pre-clinical Phase 1 Phase 2 Phase 3 Regulatory Approval Anticipated Milestones MIRA-3 Phase 3 data expected in early 2022 (n=330) MIRA-4 Pediatric safety study data expected in early 2022 (n=20) OVEGA Phase 3 program planned to initiate in mid 2022 OLYNX-1 Phase 3 data expected in early 2022 (n=140) OZETA-1 Phase 2b data expected in 2H22 (n=90-100) Seeking partner funding for IND enabling studies and further development Positive data readout Ongoing trial Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution) Ocuphire PHARMA#99 OCUPHIRE PHARMA NASDAQ: OCUP A Look Ahead Into 2022: Nyxol MIRA-3 P3 trial for RM EARLY 2022 Nyxol Pediatric trial for RM EARLY 2022 Nyxol LYNX-1 P3 trial for NVD EARLY 2022 APX3330 ZETA-1 P2b trial for DR/DME 2H22 NDA Filing for Nyxol for RM LATE 2022 RM = Reversal of Mydriasis NVD = Night Vision Disturbances DR/DME = Diabetic Retinopathy/Diabetic Macular Edema ▪ Differentiated, Late-Stage Pipeline for Front and Back of the Eye ✓ Nyxol with > 330 patients treated across 9 trials (505(b)(2) regulatory pathway) ✓ APX3330 with > 340 patients treated across 11 trials (NCE development pathway) Nyxol and APX3330 achieved promising clinical data and favorable safety profile across multiple Phase 1, 2, and 3 trials ✓ ● ● Poised for Commercial Success in Multiple Large Unmet Markets ✓ Addressing 4 large markets with unmet needs: RM, Presbyopia, NVD, and DR/DME ✓ Successful trial execution with 2 recent positive Phase 3 and Phase 2 data read-outs for Nyxol in RM and Nyxol + LDP Presbyopia, respectively ✓ Stable, small-molecule drugs with commercial scalability ✓ Robust and growing IP portfolio: US and global issued thru 2034 for both assets as well as new 2039 Nyxol patent issued for presbyopia Many Catalysts in 2022 with Track Record of Execution ✓ $24.5 million cash reported at 12-31-21 sufficient for operations into 2Q 2023 ✓ Highly experienced management, Board and KOLs with broad ophthalmic and biotech drug development and commercialization success ✓ Lower-cost, fast-enrolling, shorter-duration clinical trials ✓ Favorable, precedent regulatory environment for ophthalmic drug approval ✓ Analyst coverage by Cantor, Canaccord, Jones Trading, Alliance Global, and HCW#10DR 8 DME 10 Ų I. APX3330 Program Update INDIANA UNIVERSITY MELVIN AND BREN SIMON CANCER CENTER Mark Kelley, PhD Founder Apexian/APX3330 Cleveland Clinic Cole Eye Institute Peter Kaiser, MD Harvard Medical School Ocuphire PHARMA Retina-Vitreous Associates Medical Group David Boyer, MD Chicago Medical School#11DR DME 11 Ų APX3330 Chemistry and MOA Presented by: Mark Kelley, PhD INDIANA UNIVERSITY MELVIN AND BREN SIMON CANCER CENTER Mark Kelley, PhD Louisiana State University ● ● Ocuphire PHARMA Chief Scientific Officer and Founder of Apexian Pharmaceuticals Discovered and has developed the redox-specific inhibitors of Ref-1 for over 20 years Associate Director of Basic Science at Indiana University Simon Comprehensive Cancer Center Betty and Earl Herr Professor of Pediatric Oncology Research, Indiana University Fellow, American Association for the Advancement of Science#12APX3330 History and Ref-1 Inhibition Mechanism DME Ref-1 Involved in Multiple Key Pathways that Contribute to Diabetic Retinopathy and DME DR 12 Mechanism of Action - Ref-1 Inhibition Нурохіа Ref-1 HIF-1a VEGF (Signaling Cascade) Anti-VEGF APX3330 Neovascularization Lucentis® EYLEAⓇ 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 ● ● 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 Similar oncology origin as approved anti-VEGFs • MOA uniquely decreases both abnormal angiogenesis and inflammation by blocking pathways downstream of Ref-1 Ocuphire PHARMA#13DR DME VEGF APX3330 reduces VEGF protein expression in preclinical stroke model In vitro Validation of APX3330 Mechanism of Action APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection VEGF 13 Control % Positive area (+SE) 2.6 1.3 0.0 0.1mm VEGF T1DM-MCAO APX3330 * p<0.05 n=7/group +APX3330 APX3330 reduces pro-inflammatory cytokines in LPS stimulated macrophages TNF-α µg/mL 14000 12000 10000 8000 6000 4000 2000 0 APX3330 LPS (1 µg/mL) 14000 12000 10000 8000 6000 4000 2000 0 0 ug/mL APX3330 LPS (1µg/mL) 0 ug/mL + 6.3 ug/mL 12.5 ug/mL 25 ug/mL + 0 ug/mL 0 ug/mL + IL-6 25 ug/mL + Increasing APX3330 dose + 6.3 ug/mL 12.5 ug/mL + + % increase in APE1 repair activity APX3330 increases DNA oxidative repair and neuronal protection 120 115 110 105 100 95 N=4 *+ 12.5 25 APX3330 (μm) -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). *H 50 APX3330 enhances Ref-1 endonuclease activity in dorsal root ganglion neurons Ocuphire PHARMA#14APX3330 VEGF Effects in Normal Cells DME APX3330 Restores Normal Levels Unlike Biologic Anti-VEGFs that Reduce VEGF Below Normal DR Normal Conditions: Physiological level of VEGF activity Abnormal Conditions (e.g., hypoxic): Increased level of VEGF activity Biologic anti-VEGF agents inactivate VEGF directly and reduce VEGF levels below normal levels. Biologic Anti-VEGF Treatment APX3330 Anti-Ref-1 Treatment DM Inhibition of Ref-1 by APX3330 returns VEGF levels to normal levels. APX3330 prevents VEGF overproduction in ARPE-19 cells 14 Kamba 2007; Girardi 2010; Li 2014; APX3330 Investigator Brochure VEGF Concentrations (% of Control) 500 450 400 350 300 250 200 150 100 50 0 oxLDL APX3330 ARPE-19 cell line + * p<0.05 + 150μg/mL + 30μM 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 in over 300 subjects 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 Ocuphire PHARMA#15APX3330 Preclinical & IND-Enabling Studies DME Extensively Evaluated in Over 20 Studies by Large Japanese Pharma Eisai DR 15 Toxicology Studies 11 PK, Absorption, Distribution, & Excretion Studies APX3330 Investigator Brochure 3 Safety Pharmacology Studies 1 Geno Tox, Repro Tox & Antigenicity Studies 6 Pharmacology Models of Retinal Disease Studies Extensively Studied in Over 20 In-Vitro and Animal Studies with Favorable Efficacy and Safety 4 Ocuphire PHARMA#16DR DME 16 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 50 mg/kg Vehicle Silva et al, 2021 25 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) Day 14 ONL RPE 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) L-CNV Mouse Retina Model *EYLEA Anti-VEGF164 Vehicle CNV lesion volume (um³) 1.2x107- 9.0x106- 6.0x106- 3.0x106- 0.0 ✓ Efficacy was also seen after single intravitreal injection of 20μµM 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 Vldlrmice model*** ** Vehicle -44% Anti-VEGF164 Ocuphire PHARMA#17DR DME 17 APX3330 Human PK and Safety Summary Presented by: Peter Kaiser, MD Cleveland Clinic Cole Eye Institute Peter Kaiser, MD Harvard Medical School Ocuphire ● Chaney Family Endowed Chair in Ophthalmology Research, Professor of Ophthalmology, Cleveland Clinic Lerner College of Medicine and Cole Eye Institute Clinical research expert, serving as a Study Chairman of 5 major, multi-center, international trials, and principal investigator for numerous studies for AMD, DR, and other retinal disorders. Major contributions to medical literature having authored 7 textbooks, more than 250 peer-reviewed papers Recognized by American Academy of Ophthalmology and American Society of Retina Specialist with Senior Achievement Awards.#18DR DME Concentration of E3330 in plasma [/] 70 10 Phase 1 Clinical Trials: PK Data Supporting the ZETA-1 Trial APX3330 has Oral Bioavailability and a Sustained PK Profile 18 2 3 4 6 7 8 1. Apexian preclinical data (unpublished) 2. APX3330 Investigator Brochure 3. Eisai PK clinical data APX CLN 0002 MEAN SEM Olling :24 ~40 µg/ml (240 mg/day) in human plasma O~20 µg/ml (120 mg/day) in human plasma 2 µg/ml in mouse plasma at 2hrs; 25 mg/kg oral single dose 12 13 14 9 10 11 15 Time(day ● ● Favorable Oral Bioavailability Sustained Pharmacokinetic Profile ● Tmax 3-4 hours Linear dose-proportional PK Dose-proportional increase in Cmax/AUC exposure Half-life elimination of 45 hours (steady state [SS] 5-6 days) Meals have no clinically meaningful impact on the PK of orally administered APX3330 Sufficient APX3330 Exposure Plasma levels observed after 120 and 240 mg/day dosing is multiple times higher than what was required for efficacy in preclinical studies planned clinical dose is 600 mg/day Ocuphire PHARMA#19DR DME Phase 1/2 Clinical Trials: PK Data Supporting the ZETA-1 Trial APX3330 Reaches the Retina via Oral Administration Rat Mouse 19 ↑ Human Does oral administration of APX3330 reach the retina in sufficient concentration? 1. Orally administered, radiolabeled APX3330 reaches high levels in rat eye 25 mg/kg APX3330 oral 25 mg/kg APX3330 oral gavage measured in mouse retina Human clinical dose: 300 mg BID (600mg/day total) Established PBPK model using human data predicts APX3330 reaches sufficient human retinal concentrations APX3330 is orally bioavailable & detectable in mouse and rat retina 2. 3. Apexian preclinical data Preclinical PK and PBPK human modeling support 600 mg/day dosing for clinical development Silva et al. Oral APX3330 treatment reduces L-CNV lesions in preclinical mouse model and confirms Phase 2 DR/DME clinical dose with sufficient distribution to human retina using PBPK modeling. Presented at the ARVO 2021 Annual Meeting Eisai Preclinical Data Ocuphire PHARMA#20DR DME 20 Subject Exposure Across 11 Prior Clinical Trials Over 2000 Subject-Days of Exposure at ≥600 mg/day Total Subjects Dose: Subject-Days of Exposure Subjects with ≥21 days of exposure Subjects with >300 days of exposure 11 Trials Prior to ZETA-1 ≥600 mg/day APX3330 34* Subjects 2078 Subject-days 16 Subjects 3 Subjects <600 mg/day** APX3330 328* Subjects 17961 Subject-days 245 Subjects N/A *18 subjects in dose escalation trials received doses <600mg/day and ≥600mg/day and are included in both columns, resulting in greater than 340 subjects; **Many of the subjects between 20-240 * Eisai and Apexian Phase 1 and Phase 2 clinical trials (subject to final safety database) ** Ocuphire PHARMA#21DR DME 21 Safety Summary From Phase 1 and Phase 2 Studies Low AEs Across 11 Trials, <5% Mild Drug Related AES, Discontinuations Similar Across Arms Integrated Overall Summary of Adverse Events in Eisai Phase 2 Studies (Hepatitis) n (%) 40 (16.9%) 39 (16.5%) APX3330 20-240 mg (N=236) Rash/Pruritis (mild) 1 (0.4%) 10 (4.3%) Diarrhea/Soft Stool (mild) # events 52 50 Any event Mild or Moderate adverse Events Serious adverse events Adverse events leading to discontinuation % = proportion of subjects relative to N, where n = number of subjects with an event and N = the number of subjects in the enrolled population. Note: This table was generated by Eisai which has slightly different event and sample size counts than the Ocuphire analysis. Ocuphire will be creating an integrated safety database. The overall conclusions between the Eisai and Ocuphire analyses are the same. Phase 1 and Phase 2 Clinical Trials performed by Eisai and Apexian 2 16 Totals Across ALL Phase 1 and Phase 2 Studies (Among Healthy Subjects, Hepatitis Patients, and Oncology Patients) APX3330 Placebo n (%) 11 (16.2%) 9 (13.2%) 14/346 (4%) 14/346 (4%) Placebo (N=68) 2 (2.9%) 5 (7.4%) 2/95 (2%) # events 15 13 1/95 (1%) 2 7 *** Ocuphire PHARMA#22DR DME 22 APX3330 Product Candidate Profile for Multiple Retinal Indications First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data APX3330: Well-tolerated Oral Dose up to 600mg/day Twice Daily Dosing Expected Efficacy Data Improving Eye Health in Diabetics Inflammation ↓ Abnormal Angiogenesis Enhance Compliance & Exposure Oral pill may reduce the burden of frequent anti-VEGF injections KO Phase 1 and Phase 2 clinical trials by Eisai and Apexian Few Systemic Adverse Effects < 5% Mild Gastrointestinal (diarrhea) < 5% Mild Skin Rash (reversible) No Significant Organ Toxicity: Liver ● ● ● ● Cardiovascular (BP, HR) Kidney Neurologic Pulmonary No Ocular Effects Favorable Safety Profile ● ● No observed ocular AEs Ocuphire PHARMA#23DR DME 23 Ocuphire PHARMA APX3330 Addressing Unmet Needs in Retina Presented by: Peter Kaiser, MD#24DR DME Clinical Unmet Need in Diabetic Retinal Diseases Increasing Prevalence of DR with No Early Intervention Options • DR/DME are major causes of vision loss in working aged adults The Problem • Diabetic population expected to increase dramatically worldwide ● ● Approved therapies for DR are effective but require IVT injection DR patients are not routinely treated with approved injectable anti-VEGF drugs until they develop center-involved DME or PDR DR progresses resulting in vision loss Early, noninvasive intervention targeting DR represents a therapeutic unmet need Growing Incidence of Diabetes and DR Diabetes 34 M US >450 M WW 7 M US >150 M WW DR/DME affects about 1 in 4 people with type 1 and type 2 diabetes¹ DR 24 American Diabetes Association; International Diabetes Federation; Healthline 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 Ocuphire PHARMA#25Diabetic Retinopathy is a Progressive, Vision Threatening Disease DME Losing Vision is Diabetic Patients Top Concern DR 25 Going Blind Amputation, losing a leg Cardiovascular/heart problems Other Eye Problems Foot problems Kidney problems What are the top concerns for diabetic patients? |||||| 0% 5% 10% 15% 25% 20% 25% Percent Responders Source: Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 30% 30% 35% 35% 35% 38% 40% N=2702 40% 45% Ocuphire PHARMA#26DR DME 26 Key Clinical Landscape in Diabetic Retinopathy (and DME) Intravitreal Injection the Focus for Drugs in Development; Ocuphire Pioneering an Oral Option Company Regeneron/Bayer Roche/Novartis Roche Roche Kodiak Kalvista Eli Lilly Ocuphire Bayer Alkahest Roche Boehringer Ing. Rezolute OcuNexus OcuTerra Drug Eylea (aflibercept) Lucentis (ranibizumab) Ranibizumab PDS Faricimab KSI-301 KVD001 LY333531 APX3330 BAY1101042 AKST4290 RG7774 BI 1467335 RZ402 HCB 1019 OTT 166 Target/MOA VEGF-A/B; PIGF VEGF-A VEGF-A VEGF-A x Ang2 VEGF Plasma Kallikrein Protein Kinase C inhibitor Ref-1 inhibitor Guanylate Cyclase activator CCR3 Eotaxin inhibitor CB2 Receptor Guggenheim report (2020); www.clinicaltrials.gov; Company websites AOC3 Plasma Kallikrein Connexin 43 (inflammasome) Integrin inhibitor Route of Administration Intravitreal (DR & DME) Intravitreal (DR & DME) Surgical/Refill (DME) Intravitreal (DME) Intravitreal (DR & DME) Intravitreal (DME) Oral (DR) Oral (DR) Oral (DR) Oral (DR) Oral (DR) Oral (DR) Oral (DME) Oral (DR) Eyedrop (DR) Pre-clinical Ph1 ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ ✓ Completed O Recruiting X Discontinued/Failed study Ph2 ✓ ✓ ✓ N/A ✓ ✓ 0 X 2021 Ph3 ✓ ✓ ✓ ✓ X 2006 Commercial ✓ ✓ Oct 2021 Jan 2022 2021 Annual Sales (US/EX-U.S.) -$6 B/-$4 B -$1.5 B/-$2 B ORAL Rx Ocuphire PHARMA#27DR DME 27 ZETA-1 Phase 2b Clinical Trial (APX3330 in DR) Presented by: David Boyer, MD Retina-Vitreous Associates Medical Group Ocuphire David Boyer, MD Chicago Medical School Board-certified Ophthalmologist specializing in treatment of retinal and vitreous diseases Widely-published author and internationally recognized lecturer on retinal research and innovative approaches Investigator in numerous innovative product retinal trials over the last 35 years#28DR/DME ZETA-1 Phase 2b Design DME Ongoing, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar To Eylea P3 DR Trial) DR ZETA-1 28 25 US sites 90-100 participants with moderately severe-to-severe NPDR or mild PDR Noncentral DME is permitted Eligibility Screening 1:1 Randomization APX3330 600mg/day (BID) Week 0 Week 4 Phase 2b Initiated in April 2021 Top Line Expected in 2H22 NPDR = non-proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema) PDR = proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema) https://clinicaltrials.gov/ct2/show/NCT04692688?term=ZETA-1&draw=2&rank=1 Week 12 Placebo BID Week 24 Primary Endpoint Endpoints Primary: % of subjects with a 2 2 step improvement on the DRSS (Diabetic Retinopathy Severity Scale) score at week 24 Secondary: Central subfield thickness (CST) BCDVA (ETDRS) ● ● DRSS change at week 12 • Rescue subjects ● ● Safety and tolerability Exploratory: Labs / PK ● Ocuphire PHARMA#29DR DME 29 Key Eligibility Criteria in ZETA-1 Given Bilateral Treatment with Oral, Patient Criteria Allows DME in Fellow Eye INCLUSION ● ● EXCLUSION 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 or the presence of intra- or subretinal fluid within the central subfield ● ● ● ● Moderately-severe to severe NPDR or mild PDR in study eye as confirmed by reading center BCVA > 20/63 in study eye ● Center involved DME in the fellow eye is allowed 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 HbA1c ≥ 12.0% Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardiovascular disorders) that might interfere as deemed by Investigator ZETA-1 Clinical Trial Ocuphire PHARMA#30DR DME ETDRS Severity Level Steps Why DRSS is an Important Endpoint? FDA Accepted Endpoint for EYLEA® in PANORAMA Pivotal DR Trial - 2 Step Improvement on the DRSS Score at Week 24 30 10 | 20 1 Non-proliferative disease 2 Diabetic Retinopathy Severity Scale (DRSS) Very Mild 35 43 3 Mild Eylea® Panorama study 4 Mod 47 5 53 6 61 Proliferative disease 65 8 71 Sev. Very Mild Mod Sev. 9 75 10 85 11 High Risk PANORAMA: Reduction of DRSS Significantly reduces the incidence of Vision Threatening DR Proportion of Patients 60% 50% 40% 30% 20% 10% 0% Proportion of Patients Developing a VTC or CI-DME through Week 100 Kaplan-Meier Analysis VTC (PDR/ASNV) or CI-DME 57.7% 79% 75% 17.9% 20.5% VTC = Vision threatening complication defined as PDR/ASNV CI-DME = center involved DME % reduction in likelihood of developing the event over time^ 30.6% VTC Risk of vision-threatening events increases with worsening step progression 77% 83% 9.1% 6.9% CI-DME 38.4% 76% 11.3% 68% 14.4%* Sham 2q16 2q8 PRN *Nominal p < 0.001 vs. sham Ocuphire PHARMA#31Enrollment Update on ZETA-1 DME ~70% Completion of Enrollment in 24-week Phase 2b Trial DR 31 ZETA-1 Clinical Trial ||||| April 2021 Jan 2022 68 Patients Enrolled 90-100 target Ocuphire PHARMA#32DR DME 32 Comparison of Subject Exposure Before and After ZETA-1 ☆ Subject-Days of Exposure at 600 mg/day Substantially Increases Exposure Data Total Subjects Subject-Days of Exposure Subjects with ≥21 days of exposure Subjects with >300 days of exposure Prior to ZETA-1 34 Subjects 2078 Subject-days 16 Subjects 3 Subjects ≥600 mg/day *Assumed 50% of ZETA-1 patients are on active treatment **Many of the subjects between 20-240 mg/day +34 +3727 +27 To Date* 68 Subjects 5805 Subject-days 43 Subjects 3 Subjects *Interim Zeta-1 Data as of 01-12-22; * Eisai and Apexian Phase 1 and Phase 2 clinical trials (subject to final safety database) <600 mg/day** Prior to ZETA-1 328 Subjects 17961 Subject-days 245 Subjects N/A Ocuphire PHARMA#33Baseline Characteristics for ZETA-1 Trial (Interim) DME Typical Demographics for Diabetic Population DR 33 Parameter Age (years): mean (range) Sex: Male n (%) Female n (%) Weight (kg): mean (range) BMI (kg/m²): mean (Range) Systolic BP (mmHg): mean (range) Diastolic BP (mmHg): mean (range) Heart rate (BPM): mean (range) Source: ZETA-1 Demographics and Baseline Characteristics Total N = 68 55 (24-81) 34 (50%) 34 (50%) 84 (54-123) 30 (21-40) 137 (100-172) 80 (53-104) 76 (51-96) Ocuphire PHARMA#34Masked Safety Findings from Ongoing ZETA-1 Trial DME Favorable Safety Profile (as of 1/12/2022) Observed with 600 mg Oral Daily Doses DR APX3330 Masked Safety Data ZETA-1 Trial 34 ● 68 Randomized Subjects >3700 Subject-Days of Exposure (50% on APX3330) ● 28 Subjects with AEs (52 total events) • 52 TEAES in 28 subjects 6/52 AEs were considered probably or possibly related to study medication ● • 4 Mild (vertigo, rash, pruritus, frequent bowel movements); 2 moderate (DME*, diarrhea**) 46/52 AEs were 'not' or 'unlikely' related (32 mild, 14 moderate) 6 SAES, all unrelated to study medication 6 SAEs in 6 subjects None of these treatment emergent events were related to study medication Cellulitis, dyskinesia, transient ischemic event, COVID-19, progression of multivessel coronary artery disease, cholecystitis Only 2 subjects have withdrawn from study due to AEs: vasovagal near syncope** considered unrelated to study medication and DME* possibly study medication related (APX3330 or placebo) *same subject; **same subject Note: ZETA-1 Interim Data as of database 1/12/22 with complete monitoring before final database lock Source: ZETA-1 trial Ocuphire PHARMA#35DR DME 35 Takeaways: Masked Interim Safety Findings from ZETA-1 Trial ● ~70% completion of enrollment in 24-week ZETA-1 Phase 2b Trial No major organ toxicities (liver, heart, kidney, brain, lung) or vital sign abnormalities (blood pressure or heart rate) were observed Incidence of mild rash and diarrhea in the diabetic patient population is lower than previously observed in hepatitis patients Review of masked safety data for 600 mg/day daily dose is consistent with the favorable safety profile seen in previous studies with APX3330 ZETA-1 Clinical Trial Ocuphire PHARMA#36Broad Opportunities to Treat Retinal Diseases with APX Platform DME APX3330 May Treat Patients Across Retinal Diseases as Single Agent or Adjunctive Therapy DR 36 ● ● ● ● Potential Differentiated Solution Potential First Oral Rx for Retina Diseases First-line earlier intervention for the diabetic eye Add-on therapy to current anti-VEGF treatments to reduce intravitreal injection burden Proven Novel Mechanism May decrease both inflammation and angiogenesis Convenient Daily Regimen - - Favorable Oral Safety Profile As seen in 11 completed Phase 1 and Phase 2 clinical trials Improve Patient Compliance Potentially alleviate the frequent burden of injections - DR DME Wet AMD Dry AMD RVO GA Inflammatory component is common across these retina indications and potentially addressable by the MOA of Ref-1 APX3330 Current anti-VEGF treatments APX2009 APX2014 APX3330 (Local Delivery) Ocuphire PHARMA#37Large Global/US Market Opportunity in Retinal Disease DME Retinal US Markets Served by Anti-VEGF Injections Alone are Greater than $10B+ Today DR 37 Global Disease Prevalence (Patients) 113 M WAMD, RVO, DME combined 5 M GA 93 M DR $13 B US Revenues 1 M Dry AMD ↑ Aging ↑ Access ↑ Diabetes ↑ New Rx Products Global Forecasted Disease Prevalence (5-10 years) 130 M WAMD, RVO, DME* combined Anti-VEGF Injectable US Revenue 4% CAGR 10 M GA 110 M DR* *As early intervention options and exams are performed, there may be less DME and more DR $20 B US Projected Revenue 2 M Dry AMD Market Scope 2020 J Glob Health. 2019 Jun; 9(1): 010427 Tilahun M et. al, Prevalence of Diabetic Retinopathy and Its Associated Factors among Diabetic Patients at Debre Markos Referral Hospital, Northwest Ethiopia, 2019: Hospital-Based Cross-Sectional Study. Diabetes Metab Syndr Obes. 2020;13:2179-2187 $5+B GA Revenues $10+B Oral Rx Revenues Ocuphire PHARMA#38DR DME What's Important? APX3330 has the Potential to be 1st Line of Therapy for DR Patients Efficacy Signal Percent of patients on APX3330 with a ≥ 2 step improvement on the DRSS score at week 24 compared to placebo in 2 well-controlled, multi- center clinical trials Safety Approval depends on a product's benefit outweighing its risks in the intended population as demonstrated in, multi-center, 2 years clinical trial Non-Invasive Treatment Option FDA does not require comparative arm of approved anti-VEGF injections such as Eylea for DR 38 Eylea® label; APX3330 Investigator Brochure, ZETA-1 clinical trial FDA Guidance Physician/ Patients Efficacy Signal Clinically meaningful decrease in diabetic retinopathy severity with APX3330 Early intervention with oral may reduce progression to vision threatening DR into DME ● ● Safety 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 all eye care doctors Oral option increases global access, especially in underserved regions ● No major organ toxicities Well-tolerated (e.g., AEs acceptable if mild and infrequent for oral) ● Ocuphire PHARMA#3939 APX3330 FOR DIABETIC RETINOPATHY Question & Answer#40DR DME 40 Summary of APX3330 Program L J APX3330 is a novel orally administered drug initially being developed for DR/DME APX3330 targets Ref-1 which plays a role in signaling under both ischemic and inflammatory conditions, both of which are relevant to diabetic eye disease; resulting in inhibiting clinically validated pathways downstream of Ref-1(e.g., VEGF and inflammation) ZETA-1's masked safety findings as of 01/12/2022 support favorable safety profile of APX3330 as an oral treatment option for DR consistent with 11 prior Phase 1 and 2 clinical trials APX3330 randomized, double-masked, placebo-controlled, multi-center ZETA-1 Phase 2b trial enrollment on track at 68 subjects (of 90-100 subjects) with results expected in second half of 2022 Oral APX3330 has potential utility as adjunctive treatment with anti-VEGF injections for other retinal vascular/inflammatory diseases such as DME, GA, RVO and AMDs; future opportunities with APX2009/2014 pipeline locally or orally delivered ☆☆ Ocuphire PHARMA#41RM 41 II. Nyxol Reversal of Mydriasis Overview KENTUCKY EYE INSTITUTE Paul Karpecki, OD Indiana University Jacksoneye seeing beyond your imagination Ocuphire Mitchell Jackson, MD University of Chicago Ocuphire PHARMA Bindu Manne Head of Commercialization#42RM 42 KENTUCKY Reversing Dilations: Addressing an Unmet Need with a1 Blocker Nyxol Presented by: Paul Karpecki, OD EYE INSTITUTE Paul Karpecki, OD Indiana University Ocuphire ● PHARMA Director of Cornea Services for Kentucky Eye Institute, Gaddie Eye Centers, Midwest Center for Sight Associate Professor at the Kentucky College of Optometry and Board Member of Optometry Giving Sight Medical Director for KEPLR Vision and Dry Eye Institutes of Kentucky and Indiana Chief Medical Editor for Review of Optometry, Chairman of the NTT Conferences#43RM 43 Problem: Dilated Eyes for Exams and Procedures Patients Report Significant Side Effects after Dilated Eye Exam The Problem Pharmacologically-induced pupil dilation is a necessary tool for routine ophthalmoscopy... ...but there is 6 to 24 hours of impaired vision including: Inability to Focus ● ● Photophobia (sensitivity to light) Cycloplegia (loss of accommodation) Difficulty Reading and Driving Halos and Glare 1. GlobalData Market Research Survey; Oraverse and Regitine Label Physician's Use of Mydriatic Agents¹ Cyclopentolate 5% Paremyd 9% Phenylephrine Alone 16% Tropicamide and Phenylephrine 18% Tropicamide Alone 52% Note - Tropicamide and Cyclopentolate have same MOA NO REVERSAL DROPS COMMERCIALLY AVAILABLE Ocuphire PHARMA#44RM 44 Current Off-Label Landscape for RM Physicians AVOID Use of Cholinergic Agonists (Pilocarpine) Due to the Risk on Ciliary Muscle 2 Classes of Mydriatic Agents Phenylephrine (a1 agonist) Sympathetic (primarily a1) innervation stimulates the iris dilator muscles Tropicamide (anti-cholinergic) Parasympathetic innervation stimulates the iris sphincter and ciliary muscle Lens Corneal Pupil Iris Ciliary muscle Reversal via the Ciliary Muscle by Cholinergic Agonists* is Not a 'Safe' Option 1. Optician (2012)- Mydriatic Drugs: Practical Considerations 2. Pilocarpine FDA Label (2017) 3. Lee DA, Higginbotham EJ, 2005. Glaucoma and its treatment: a review. Am J Health Syst Pharm 62, 691-699. X X X Induces accommodation spasm and reduction in distance vision¹ Induced anterior shift of the lens can increase the risk of acute angle-closure glaucoma¹ High incidence of brow ache and headache following installation³ Retinal tear has been reported in some patients² * Cholinergic Agonists include pilocarpine, carbachol, and aceclidine. Note, pilocarpine is rarely used off-label for RM given these safety concerns. Nyxol® is the only eye drop in clinical development for multiple indications that does not affect the ciliary muscle Ocuphire PHARMA#45Nyxol's Differentiated MOA as an Alpha-1 Blocker RM Phentolamine Mesylate Reformulated as a Proprietary Topical Eye Drop → Nyxol 45 Phentolamine Mesylate is the Active Ingredient in Nyxol: a Non-selective a1 & a2 Antagonist Blocking a1 Blocking a1 Reduces Pupil Size Dilates Blood Vessels Iris Dilator Muscle Iris Sphincter Muscle Ocuphire Nyxol blocks a1 receptors only found on the Iris Dilator Muscle Decreases Pupil Size (Moderate Miosis) without Affecting the Ciliary Muscle Phentolamine mesylate is approved for 2 indications: ● A ● Regitine® (Pheochromocytoma) - intravenous injection approved in 1952 OraVerse® (Reversal of oral anesthesia) - intramuscular injection approved in 2008 505(b)(2) Regulatory Approval Pathway Ocuphire PHARMA#46RM 46 Nyxol Product Candidate Profile Novel, Differentiated Alpha 1/2 Blocker Eye Drop for Refractive Indications Effective Nyxol: 0.75% Phentolamine Ophthalmic Solution Preservative Free, EDTA Free, and Stable Favorable Safety Profile Nyxol Improves Vision by Decreasing Pupil Size (1 to 1.5mm) Nyxol Clinical Trials ↑ Near & Distance Visual Acuity ↑ Contrast Sensitivity (night) No Systemic Effects No Changes in Blood Pressure No Changes in Heart Rate Well-Tolerated Topical Effects Mild, Transient, Reversible Eye Redness IOP Unchanged or Decreased No Headaches Favorable safety profile vs competitors Durable Effects Last ≥ 24 Hours Chronic daily dosing of Nyxol at bedtime reduced pupil size for up to 24 - 36 hours With nighttime use, patients wake up without eye redness Ocuphire PHARMA#47RM 47 Ocuphire Nyxol Clinical Data for Reversing Dilations Presented by: Paul M. Karpecki, OD#48RM 48 MIRA Program Evaluating Nyxol for the Reversal of Mydriasis Efficient Clinical Programs have Positioned Ocuphire to Target NDA Filing in Late 2022 MIRA-1 2019 Phase 2b n=32 crossover Ocuphire Primary Endpoint Met ✓ Secondary Endpoints Met ✓ MIRA-2 2021 Phase 3 n=185 Primary Endpoint Met ✓ Secondary Endpoints Met ✓ MIRA-3 2022 Phase 3 n=330 MIRA-4 2022 Pediatric Safety n=20 RM NDA Filing 2022 NDA Submission Ocuphire PHARMA#49RM 49 MIRA-2/3 Phase 3 Registration Trial Design Randomized, Double-Masked, Placebo-Controlled, Parallel, One-Day Trial 12 to 16 US sites 185 to 330 target healthy subjects Eligibility Screening 0.75% Nyxol 1:1 2:1 Placebo Randomization Mydriatic Agent A, B, or C Mydriasis -1 Hour Treatment (Max Dilation) 0 min Mydriatic Agent A, B, or C 1 Hr 30min Nyxol drop(s) (2 drops study eye, 1 drop fellow eye) 2 Hr 3 Hr 90min Placebo drop(s) (2 drops study eye, 1 drop fellow eye) Enrollment MIRA-3 Started in 4Q21 Topline Results Expected in Early 2022 4 Hr Follow Up Visit 6 Hr 24 Hr Mydriatic Agents 3:1:1 - 2.5% phenylephrine (alpha-1 agonist), 1% tropicamide (cholinergic blocker), Paremyd® (combination) Endpoints Primary: % of subjects (study eye) returning to baseline (within 0.2 mm) photopic pupil diameter (PD) at 90 min Secondary: ● ● ● ● ● % of subjects returning to baseline at Omin, 30min, 1h, 90 min 2h, 3h, 4h, 6h, 24h (overall, by mydriatic agent, by iris color) Mean change in pupil diameter at all timepoints Accommodation (Tropicamide/Paremyd) Visual acuity & discomfort w/ glare Pupillary light reflex Safety and tolerability (redness) Ocuphire PHARMA#50RM 50 MIRA-2: Participant Characteristics MIRA-2 Study was Balanced Across Both Nyxol and Placebo Groups Age (years): Median (Range) Sex: Male n (%) Female n (%) Race: White n (%) African American n (%) Asian n (%) Other^ n (%) ^includes American Indian or Alaska Native; Native Hawaiian or Other Pacific Islander Dark Iris Color: n (%) Light Iris Color: n (%) Baseline Pupil Diameter Mean (mm) Max Dilated Pupil Diameter Mean (mm) Nyxol n=94 31 (12-70) Source: MIRA-2 TLR table # 14.1.2.3 (mITT) 36 (38%) 58 (62%) 70 (75%) 17 (18%) 6 (6%) 2 (2%) 49 (52%) 45 (48%) 5.09 7.21 MIRA-2 Phase 3 Trial Placebo n=91 30 (13-73) 36 (40%) 55 (60%) 7.28 74 (81%) 16 (18%) 3 (3%) 1 (1%) 46 (51%) 45 (50%) 5.18 Accommodation Median (diopters) Note: 14 pediatric subjects 12-17 years old were enrolled in the trial; Race is more than 100% given subjects could check more than one category. 7.20 7.41 Total n=185 31 (12-73) 72 (39%) 113 (61%) 144 (78%) 33 (18%) 9 (5%) 3 (2%) 95 (51%) 90 (49%) 5.13 7.20 7.41 Ocuphire PHARMA#51RM 51 MIRA-2: Phase 3 RM Trial Met Primary Endpoint 49% of Patients Returned to ≤ 0.2mm of Baseline at 90 Minutes Percent of Subjects (%) 100% 80% 60% 40% 20% 0% MIRA-2 Phase 3 Trial Nyxol Reduced More Subjects to Baseline Pupil Diameter (PD) at Every Timepoint Placebo n=91 Nyxol n=94 3% 1% 0.5 2% Study Eye Percent of Subjects Returning to ≤ 0.2 mm of Baseline PD p<0.0001 28% 1 7% p<0.0001 49% 1.5 11% p<0.0001 59% 2 18% Time Post-Treatment with Nyxol/Placebo (Hours) Source: MIRA-2 Trial Table 14.1.2.1, mITT Population (same as Safety Population) *Data includes three of the most common mydriatics used in practice (Phenylephrine, Tropicamide, Paremyd) p<0.0001 80% 3 30% p<0.0001 82% 4 45% p<0.0001 90% CO 6 Ocuphire PHARMA#52RM 52 Percent of Subjects (%) MIRA-2: Study Eye and Non-Study Eye Similar Rapid Return to Baseline Pupil Size Results with 1 or 2 Drops of Nyxol 100% 80% 60% 40% 20% 0% MIRA-2 Phase 3 Trial 1 or 2 Drops Nyxol Reduced More Subjects to Baseline Pupil Diameter (PD) at Every Timepoint Non-Study Eye (1 Drop) Study Eye (2 Drops) Percent of Subjects Returning to ≤ 0.2 mm of Baseline PD Percent of Subjects Returning to ≤ 0.2 mm of Baseline PD Placebo n=91 Nyxol n=94 3% 1% 0.5 p<0.0001 2% 28% 1 p<0.0001 49% 7% 1.5 p<0.0001 59% 11% 2 p<0.0001 80% 18% 3 p<0.0001 82% 30% 4 Time Post-Treatment with Nyxol/Placebo (Hours) p<0.0001 90% 45% 6 Percent of Subjects (%) 100% 80% 60% 40% 20% 0% Source: MIRA-2 Trial Table 14.1.2.1, mITT Population (same as Safety Population) *Data includes three of the most common mydriatics used in practice (Phenylephrine, Tropicamide, Paremyd) Placebo n=91 Nyxol n=94 2% 2% 0.5 p=0.003 6% 25% 1 p<0.0001 49% 6% 1.5 p<0.0001 51% 10% 2 p<0.0001 68% 14% 3 Time Post-Treatment with Nyxol/Placebo (Hours) p<0.0001 76% 24% 4 p<0.0001 86% 45% 6 Ocuphire PHARMA#53RM Percent of Subjects (%) MIRA-2: Responders Returning to Baseline Pupil Size by Iris Color Nyxol Works in Subjects with Both Light and Dark Irides, with a More Vigorous Response in Light Irides 53 100% 80% 60% 40% 20% 0% Placebo n=45| Nyxol n=45 Light Irides (Study Eye) Percent of Subjects Returning to ≤ 0.2 mm of Baseline Placebo n=45 ■Nyxol n=45 0.5 0% 0% p<0.01 1 0% 31% p<0.0001 p<0.0001 Nyxol Reverses Dilation in Light and Dark Irides MIRA-2 Phase 3 Trial p<0.0001 || 1.5 2 3 4 2% 7% 13% 89% 24% 96% 56% 71% Time Post-Treatment with Nyxol/Placebo (Hours) p<0.0001 p<0.0001 6 49% 93% 100% 80% 60% 40% 20% 0% Placebo n=46 Nyxol n=49 Source: MIRA-2 TLR table #14.2.1.6 (MITT) *Data includes three of the most common mydriatics used in practice (Phenylephrine, Tropicamide, Paremyd) Dark Irides (Study Eye) Percent of Subjects Returning to ≤ 0.2 mm of Baseline Placebo n=46 Nyxol n=49 0.5 7% 2% p<0.01 p<0.001 1 4% 25% p<0.001 1.5 11% 43% 2 3 15% 22% 47% 71% Time Post-Treatment with Nyxol/Placebo (Hours) p<0.0001 p<0.001 4 35% 69% p<0.0001 6 41% 88% Ocuphire PHARMA#54RM 54 MIRA-2: Mean Pupil Size Over Time After Maximum Pupil Dilation Nyxol Treatment Significantly Reduced PD Starting at 1 Hour Post-Dose through 24 Hours Mean Pupil Diameter (mm) 8 7 5 Mydriatic 4 3 -1 Max pupil dilation Nyxol Reduced PD Faster Across All Mydriatic Agents* Study Eye Mean Pupil Diameter Treatment Administered 0 0.5 p<0.0001 1 11 p<0.0001 p<0.0001 MIRA-2 Phase 3 Trial 2 p<0.0001 3 p<0.0001 4 5 Time Post-Treatment with Nyxol/Placebo (Hours) Source: MIRA-2 TLR table # 14.2.2.1 (mITT). Standard Error bars are shown. *Data includes three of the most common mydriatics used in practice (Phenylephrine, Tropicamide, Paremyd) p<0.0001 6 Nyxol n=94 Placebo n=91 p<0.0001 24 Ocuphire PHARMA#55RM 55 MIRA-2: Mean Pupil Diameter Over Time by Mydriatic Agent Nyxol Reduced Pupil Diameter with All Mydriatic Agents; More Rapidly with Phenylephrine as Expected Pupil Diameter (mm) 9 8 4Mydriatic 3 Max pupil dilation, Treatment -1 Phenylephrine (Study Eye) Mean Pupil Diameter p<0.0001 p<0.0001 0 0.5 1 p<0.0001 MIRA-2 Phase 3 Trial Nyxol Reduced PD Faster Across All Mydriatic Agents F4 KA p<0.0001 p<0.0001 K Nyxol n=56 Placebo n=55 p<0.0001 2 3 4 Time Post-Treatment with Nyxol/Placebo (Hours) 6 Source: MIRA-2 TLR table #14.2.2.3 (mITT). Standard Error bars are shown. p<0.0001 24 Pupil Diameter (mm) 9 8 3 Mydriatic -1 Tropicamide or Paremyd (Study Eye) Mean Pupil Diameter p<0.0001 Max pupil dilation, Treatment p<0.0001 0 0.5 1 p<0.0001 H p<0.0001 F 1 p<0.0001 -Nyxol n=38 Placebo n=36 HA p<0.0001 5 2 3 4 Time Post-Treatment with Nyxol/Placebo (Hours) 6 7 p<0.0001 24 Ocuphire PHARMA#56RM Percent of Subjects (%) 56 MIRA-2: Gain of Visual Function (Accommodation) Nyxol Demonstrates a Faster Return to Baseline Accommodation Percent of Subjects with Unchanged Accommodation from Baseline (Tropicamide or Paremyd) Study Eye, PP population Placebo (n=32) Nyxol (n=35) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 16% 11% 0 p=0.03 38% 60% 2 Time Post-Treatment with Nyxol/Placebo (Hours) MIRA-2 Phase 3 Trial Note: Worsening of accommodation was defined as an amplitude decrease of greater than 1 diopter Source: MIRA-2 CSR table #14.2.3.2.1. PP population is the per protocol population. Patel (2011). Pseudoaccommodation. International Ophthalmology Clinics, 51(2), 109-118. ● ● ● Accommodation Definition: Changing optical power to maintain a clear image or focus on an object as the distance varies Inhibition of the cholinergic system dilates the pupil (mydriasis) and relaxes the ciliary muscle, which adjusts the lens shape and thickness, worsening accommodation (cycloplegia) and causing latent refractive errors to manifest Mydriatic agents including Tropicamide and Paremyd inhibit the cholinergic system; not seen with Phenylephrine Nyxol ✓ Nyxol, a non-selective, alpha-1 antagonist, constricts the pupil enhancing depth of focus by blocking unfocused peripheral light, independent of the ciliary muscle Ocuphire PHARMA#57RM 57 MIRA-2: Safety Findings (After Dilation with Mydriatic Agent) Nyxol was Well Tolerated with a Favorable Safety Profile Total Treatment Emergent Adverse Events (n) TEAES by Severity (n [%]) Mild Moderate Severe AES Occurring in ≥ 5% of subjects (n [%]) Instillation Site Discomfort Conjunctival Hyperemia Conjunctival Hyperemia (mean [SD]) Baseline (-1 hour) 60 minutes after instillation of Nyxol 4 Hours after instillation of Nyxol Conjunctival Hyperemia Grading Scale (CCLRU) None (0) Nyxol n=94 113 47 (50%) 3 (3%) 0 (0%) 36 (38%) 12 (13%) 0.7 (0.6) 1.7 (0.5) 1.2 (0.7) Mild (+1) Placebo n=91 31 15 (17%) 0 (0%) 0 (0%) 8 (9%) 0 (0%) 0.7 (0.5) 0.5 (0.5) 0.5 (0.5) Moderate (+2) Total n=185 144 62 (33%) 3 (2%) 0 (0%) 44 (24%) 12 (7%) 1 1 1 Severe (+3) There were no deaths, serious AES, or withdrawals due to AEs 94% of the AEs in the Nyxol group were mild Installation site discomfort was 97% mild; No burning, no stinging, no ptosis upon installation From a baseline mean of 0.7, the mean hyperemia score increased by approximately 1.0 unit (on a 4-point scale) at 60 minutes post-dose and decreased steadily thereafter Source MIRA-2 Safety Population TLR table 14.3.1.1.; MIRA-2 table 14.3.1.2.2 System Organ Class; MIRA-2 table 14.3.3.2 Hyperemia Score by Time Point Ocuphire PHARMA#58RM 58 NDA Submission Targeted in Late 2022 Ongoing Activities Sets Ocuphire on Path to a Potential Regulatory Approval in 2023 Target Label Indication The treatment of pharmacologically induced mydriasis produced by adrenergic (e.g., phenylephrine) or parasympatholytic (e.g., tropicamide) agents, or a combination thereof. Preservative-Free Single Unit Vial (5-pack) NyxolⓇ Topline Results Expected in Early 2022 P3 Clinical Trial Complete a 2nd Phase 3 trial in RM with ~330 subjects which also meets 24-hour safety population exposure 4141 Pediatric Safety Complete RM trial with 20 subjects ages 3 to 11 per agreed FDA initial pediatric plan : Manufacturing Completed 3 registration batches; 1-year CMC stability for NDA Regulatory Approval Submit NDA by Late 2022 Ocuphire PHARMA#59RM Efficacy Signal Statistically significant percent of subjects on Nyxol compared to placebo returning to baseline (within 0.2 mm) photopic pupil diameter (PD) at 90 min demonstrated in 2 well-controlled, multi- center clinical trials Precedent set with RevEyes Approval ● Safety ● What's Important? Nyxol has the Potential to be the only FDA-Approved Treatment Option to Reverse Dilation ● 59 Well-tolerated drop No significant ocular or systemic AES or SAEs Label Expansion Opportunity to expand label with ongoing pediatric trial in kids 3 years and up given safety shown in dental reversal approval for phentolamine FDA Guidance Physician/ Patients Efficacy Signal Compelling magnitude of response compared to placebo with statistical significance More rapid response with Nyxol vs. placebo Works in all iris colors Works across all commonly used mydriatic agents ● ● Safety No systemic side-effects such BP, HR, headache Mild, transient hyperemia is acceptable and common in Rx drops ● Patient Experience Patients desire more rapid return to normal activities Patients actively asking for 'reversal' drops Patients want a comfortable experience post-dilation Patients more likely to maintain their annual exams if option to reverse dilation is presented ● ● ● Ocuphire PHARMA#60RM 60 RM Market Opportunity and Commercialization Presented by: Mitchell Jackson, MD Jacksoneye seeing beyond your imagination Mitchell Jackson, MD University of Chicago ● Ocuphire ● Founder and CEO of Jacksoneye in Illinois 29 years of experience as a Comprehensive Ophthalmologist 2021 Best Cataract Surgeon in America 2021 - Top 50 Global Key Opinion Leaders (KOL)#61RM 61 Patients are Vocal About the Negative Effects of Mydriasis "I hate having my eyes dilated" generated thousands of results on Google, Social Media and Patient Forums "It takes all day or sometimes overnight to return to normal! I have too much to do!" "I have to visit my retina MD for my monthly injections, where I am dilated. Being dilated every month is a huge burden on my day." }} Quotes are from anonymous patients (1 (1 "I hate going to the eye doctor. Ruins my whole day." "Ever since I was a little kid, I have hated getting my eyes dilated. I hate trying to walk, let alone try to drive in the sun with dilated eyes." " "I HATE having my eyes dilated. Every time=migraine" "I had a premium cataract procedure by my MD, and I was unable to see clearly for two days. My doctor said it was due to my dilation. I did not expect my dilation to last that long." Ocuphire PHARMA#62RM 62 Importance of Dilations Dilated Eye Exam Remains the Recommended Standard of Care AMERICAN ACADEMY™ OF OPHTHALMOLOGY Patient Types For Dilation • Patients with or at-risk for glaucoma, diabetes, AMD, etc. • Patients undergoing cataract evaluation ● • Patients undergoing refractive evaluation (includes first or annual exams) • Patients receiving anti- VEGF injections AMERICAN ACADEMY of OPTOMETRY Anyone over the age of 60 or other risk populations ● CDC CENTERS FOR DISEASE CONTROL AND PREVENTION ● • Photophobia Blurry vision Reasons Patients Decline Headaches Advocacy A Allergic reactions • Digital strain Phobia Loss of accommodation • Lifestyle American Diabetes Association® Work AMERICAN OPTOMETRIC NIH ASSOCIATION Non-Dilated Exam ● • Ultra-Widefield Imaging (UWFI) Tool ● National Eye Institute Research Today...Vision Tomorrow Barriers: - Capital Equipment Cost - Training time - Cost to patient $40-80 - Not a replacement for a dilated exam - Dilated exam is standard of care Source: American Academy of Ophthalmology, Comprehensive Adult Medical Eye Evaluation Preferred Practice Pattern, 2020 $35 B+ Societal cost of major visual disorders among U.S. residents aged 40+ 63% of participants who had eye disease were not aware Ocuphire PHARMA#63RM Demand Side Estimate TUZ LPED. PECTD. EDFOZP Bottom-Up Calculation of Annual Dilated Eye Exams ~101 Million Annual Dilated Eye Exams are Performed in the US 63 Optometrists Ophthalmologists Retina Specialists Number of Providers (X) 46,000 18,000 3,000 Average Number of Weekly Exams (Y) 59 88 150 Estimated % Patients Dilated (Z) *IQVIA 2020 sales data; KOL Interview; GlobalData market research; and AOA Excel and Jobson Medical Information 'Bottom-Up Calculation' assumes 48 total work weeks in a year Supply side validation assumed each unit (bottle) has ~10 mL fill volume and each patient gets 2-4 drops 40% 50+% 50% Total (X*Y*Z)* 48 wk/yr ~52 M ~38M ~11 M 101 M Annual Dilated Eye Exams Supply Side Validation: Based on the ~2 million total units of mydriatic agents sold in 2020, we calculated the total number of dilated eye exams to be ~125 million patients, consistent with demand side estimates. Ocuphire PHARMA#64RM 64 ● Market Research Methodology by Global Data Market Research Conducted in 2H 2020 for RM, Presbyopia, and Night Vision Disturbances GlobalData conducted this research in 4 phases of primary research, which allowed us to inform the survey instruments for each audience as the project progressed 1 Physician Perceptions OBJECTIVE: Assess the competitive environment in each of the three indications from the perspective of treating physicians ● Payer Patient Perceptions Perceptions OBJECTIVE: Understand the assignment of coverage in pharmacy or vision plans 3 GlobalData Market Research Survey OBJECTIVE: Understand patients' current unmet needs as well as their potential acceptance of or desire for Nyxol . Quantitative Physician Input OBJECTIVE: Quantitatively assess the potential use of Nyxol in each of the three indications MMMM >200 Total Patients Surveyed Reversal of mydriasis (N=190) Presbyopia (N=134) Dim Light Vision Disturbance (N=120) ● 120* Optometrists & Ophthalmologists Surveyed (N=69 Optometrists; N=51 Ophthalmologists) * Retina specialist were not surveyed Ocuphire PHARMA#65RM 65 Reversal of Mydriasis (RM) Market Opportunity With No Commercially Available Treatment, Nyxol may Achieve Significant Revenue Potential Global Data Market Research Findings 101M Annual Dilations 95% of Dilating Drops Used by ECPs 80% of Patients Likely to Request Drop Source: GlobalData Market Research Survey 65% Report Moderate to Severe Impact to Daily Function Patient Willingness to Pay $10 to $20+ $500+M Estimated US RM Market Opportunity 58% physicians would start prescribing Nyxol within 1st year 81% patients would be more likely to schedule yearly eye exams with a reversal drop 0 Current Commercially Available Treatments 68% physicians would be willing to use Nyxol even if patients had to still wear sunglasses within 1st hour Ocuphire PHARMA#66RM 66 Why 1990' Rev-Eyes is Not a Benchmark for Nyxol Future RM Sales Nyxol's Broad Differentiation Addresses the Unmet Need for Reversal Drops in New Era 010 Efficacy Safety Stability Commercialization ● ● ● ● ● Problems with Rev Eyes 4 drops from a multiuse office bottle (added additional chair time) Significant Side-effects ● ● Rev-Eye label; Nyxol clinical trials Burning and stinging sensation Ptosis 'beefy red eyes' Nicknamed "Red-Eyes" Not an acceptable commercial formulation Burden of preparation given requirement to mix at physician office Product stable for only 21 days Limited marketing effort Years of being on-and-off the market given multiple pharma owners hindered uptake ● Nyxol Differentiation 1 to 2 drops for a rapid reversal from a single- unit vial No burning and stinging sensation No ptosis 94% of AEs were mild A hassle-free, room temperature shelf-stable, sterile, preservative-free, single-unit vial Experienced team committed to commercial success in RM Expected growth in dilations due to an aging population and digital dependence Ocuphire PHARMA#67RM 67 RM Market Opportunity and Commercialization Presented by: Bindu Manne Ocuphire Bindu Manne Head of Commercialization Ocuphire Pharma Ocuphire ● 16 years of experience primarily in product launches (12+) across all ophthalmic specialists Dynamic experience ranging from sales, market development, professional and medical affairs Ophthalmic World Leader: Rising Star Award Recipient Non-Profit Board Member: Holland Foundation For Sight Restoration and Ophthalmic World Leaders#68RM 68 ● ● ● Perspective from Practice Administrators on Reversing Dilations Leading Practice Administrators Confirm the 'Market Need,' and Value to Patient Anterior Segment Practice in Southeast "We've explored and offered several options over the years to reverse mydriasis - both as a tool to elevate the patient experience and to reduce liability when a patient with poor accommodation walks out of my practice. We've used pharmacologic agents to reverse the effects of dilation in the past, but those products had significant limitations, and I would welcome a new option indicated for RM in my practice." - Certified Ophthalmic Executive and CEO Multi-Specialty Practice, Midwest "We call our patients guests so anything to enhance their experience is valuable for our practice. Pupil dilation is a perceived inconvenience - especially for the working- age population. They grab up our evening appointments typically, so they don't have to go back to work while dilated. Having an option to reverse dilation is something we and our guests would enjoy." - Certified Ophthalmic Executive and CEO Leading Academic Eye Center "Patients have anxiety over dilation and if we could reduce that fear, help them regain accommodation faster, I would like to consider that option across all specialties." - Head of Operations, Certified Practice Administrator Interviews Conducted by Ocuphire Willingness to Implement: We would be comfortable passing this cost to the patient as a premium to resume visual function faster. N Patients would be willing to pay for this benefit. Ocuphire PHARMA#69RM 69 Pre-Commercial Activities in 2022 Activities Underway to Support Capital-Efficient Nyxol RM Commercial Launch Market Development Engage leading Key Opinion Leaders and Professional Societies to establish our commitment to refractive and retinal disorders Patient Journey Establish Ocuphire as a patient-centric company and leader in improving everyday vision through education to empower purchasing decisions Physician Targeting Broad HCP opportunity with focus on early adopters to capture post-market data and patient experience Eye Care Practitioners in U.S. Total Ophthalmologists Total Optometrists Total Retina Specialists Brand Awareness Across Eye Care Professionals 18,000 46,000 3,000 Initiate branded and unbranded education for ophthalmologists, optometrists and practice professionals Ocuphire PHARMA#70RM 70 Go-To-Market Strategy for 2023 Nyxol as RM Allows Efficient Pharmaceutical Launch Across Eye Care Practices Ocuphire Preferred Go-To Market Strategy for 2023 Partner with existing commercial sales and distribution players that have established ophthalmic products and relationships An Efficient Launch... * No approved drug/competition * * Routine part of practice Patients daily function impacted by eye dilations Ocuphire PHARMA#71RM 71 Practice Implementation Models Positive Feedback from Physicians on Integration of a Reversal Agent into Practice Optometry TON LPED. PECFD EDTCZP FELOPED DEFPOTRO Ophthalmology PO Retina Adoption into practice requires no additional staff or patient training Practices across all specialties expressed the positive impact on patient experience and adherence to dilated exams Physician Interviews Conducted by Ocuphire Ophthalmology and Optometry practices would pass a nominal fee into their routine refraction and include it in their surgical pricing Retina practices across academic centers favored offering to patients at no additional cost due to the volume of dilated exams and as a patient satisfaction service Ocuphire PHARMA#7272 Nyxol® for Reversal of Mydriasis (RM) QUESTION & ANSWER Ocuphire PHARMA#73RM 73 Summary of Nyxol Reversal of Mydriasis Program Nyxol, the first ophthalmic formulation of phentolamine mesylate, is a differentiated MOA uniquely suited for reversal of pharmacologically-induced mydriasis c In MIRA-1 and MIRA-2, Nyxol met its primary endpoint of rapidly returning subjects as well as many key secondary endpoints Consistent with prior trials, Nyxol has demonstrated favorable safety and tolerability with a MOA uniquely suited to avoid safety issues associated with cholinergic drug (e.g. pilocarpine) reversal of dilations MIRA-3 Phase 3 and MIRA-4 Pediatric Safety trials are currently enrolling patients at 15 sites in the US with data expected in early 2022 We anticipate the results of these trials will support an NDA submission for Nyxol in late 2022 Nyxol has the potential to be the ONLY commercially-available, FDA-approved Rx treatment to reverse pupil dilation in a growing $500+M US Market Ocuphire PHARMA#74P 74 P C 0.4% III. Nyxol Presbyopia Program PeposeVision INSTITUTE Jay Pepose, MD, PhD UCLA School of Medicine Ocuphire PHARMA the Midwest Center for Sight James Katz, MD University of Illinois, College of Medicine#75P 75 Pupil Modulation Eye Drops for Presbyopia Presented by: Jay Pepose, MD, PhD PeposeVision INSTITUTE Jay Pepose, MD, PhD UCLA School of Medicine ● Ocuphire ● Founder and Medical Director of Pepose Vision Institute Founder of Midwest Vision Research Foundation Recognized Thought Leader in Ophthalmology 40 Years of Experience as a Treating Physician and Widely Published Researcher#76P The Time for Presbyopia Drops Headlines from Academia and Industry Articles with an Early First Approval for Vuity™ September 22, 2021 | 11 min read Treatment landscape for presbyopia evolving toward noninvasive options Presbyopia PHYSICIAN In the Face of Presbyopia... A New Conversation is Imminent 76 New options are on the horizon for presbyopia-correcting drops August 30, 2021 Dr Marguerite B. McDonald Ophthalmology Times Europe Journal, Ophthalmology Times Europe September 2021, Volume 17, Issue 07 How ophthalmic leaders view solutions today and those on the horizon SAVE Article By Conni Bergmann Koury July 1, 2021 Presbyopia treatment options now and on the horizon "The correction of presbyopia remains ophthalmology's 'Holy Grail'..." Refractive September 2021 -OIS Presbyopia-correcting drops: The next frontier Pharmaceuticals are poised to enhance near vision for millions of presbyopes. Sources: Academic review articles, journals, and publications Clinical Ophthalmology FDA APPROVAL OF ABBVIE EYE DROP A NEW MOMENT IN PRESBYOPIA 10/29/2021 Presbyopia - A Review of Current Treatment Options and Emerging Therapies Dovepress CLINICAL UPDATE REVIEW Presbyopia-Correcting Eyedrops Move Ahead Presbyopia PHYSICIAN NOVEMBER 2021 HELP ON THE WAY ent options the corner CBS News New FDA-approved eye drops could replace reading glasses for millions: "It's definitely a life changer" Presbyopia Treatment Market Size Projected to Rise Lucratively by 2026 end BioSpace PentaVisien How Presbyopia Correction Drops Will Change My Treatment Regimen CRST Cataract & Refractive Surgery Today#77P 77 What is the Optimal Pupil Size? Literature Highlights New Drops to Treat Presbyopia Achieve Optimal Pupil Diameter of 2-3 mm VSTOF (Constricted/natural) 100 10 0.1 Photopic Lighting (100 -1000 lux) Natural Pupil Size ~ 4 mm 0% NEAR Vision DISTANCE Vision Optimum 2.0-3.0 mm 20% 60% 80% % Constricted Pupil Size of Natural Pupil 40% TT Natural Pupil 100% Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic Eyes Renfeng Xu*, Larry Thibos, and Arthur Bradley* "A fixed 2- to 3-mm small pupil or a 30% pupil miosis can both produce near visual acuity gains without significant losses to distance acuity or image quality, and therefore can be considered as optimal for a presbyope experiencing a wide range of light levels." - Optometry and Vision Science, November 2016 WHAT IS THE OPTIMAL PUPIL SIZE? OF This question is becoming increasingly relevant as small-aperture IOLs and pupil-modulating drops are developed to treat presbyopia. BY JAY S. PEPOSE, MD, PHD, AND RENFENG "RENA XU, MD, PHD CATARACT SURGERY "The impact of pupillary modulation on the functional depth of field differs among patients with refractive error versus those who are truly emmetropic. "" - Cataract & Refractive Surgery Today (CSRT), January 2022 Source: Xu et al, OVS 2016; Pepose & Xu CSRT article 2022, Effect of Target Luminance on Optimum Pupil Diameter for Presbyopic Eyes Ocuphire PHARMA#78P 78 0.4% Ocuphire PHARMA Nyxol with LDP as Adjunctive Therapy in Presbyopia Presented by: Jay Pepose, MD, PhD#79Nyxol® with Low-Dose Pilocarpine (LDP) as Adjunct Therapy Moderate Action on Iris Dilator and Iris Sphincter Muscles for Near Vision Improvement 0.75% Nyxol P 79 + Flo C 0.4% 0.4% LDP Iris Dilator Muscle Inhibition Iris Sphincter Muscle Activation Source: 1) Nyxol® data from 9 completed trials; Pilocarpine Product label and Literature Evening drop Daytime drop ● ● ● ●. ● ● ● ● ● Phentolamine (alpha1/2 antagonist) Novel MOA on iris dilator with 24+ hour durability Moderate 1+mm pupil reduction No daytime redness Well-tolerated with no systemic effects Stable, preservative-free, single-use vial Pin-hole target is 2 to 3 mm with contributions from each MOA Pilocarpine (cholinergic agonist) Known MOA on sphincter (and ciliary) muscle as potent miotic at approved doses (1%, 2%, 4%) Low concentration avoids known safety issues: ➤ headache and browache ➤ redness ➤ accommodative spasm causing loss of distance vision especially at night Ocuphire PHARMA#80VEGA-1: Presbyopia Phase 2 Trial Design P Randomized, Double-Masked, Placebo-Controlled, Multi-Center One-Week Trial 80 ● ● ● VEGA-1 17 US sites 150 presbyopic patients 0.75% Nyxol arms Placebo Randomization Visit 1 (Day 1) Baseline Baseline Baseline Baseline Screening Evening Dosing (3-4 doses) Nyxol Nyxol Placebo Placebo Visit 2 (Day 5) LDP Drop No Treatment LDP Drop No Treatment Treatment Arms Nyxol + LDP Nyxol Alone LDP Alone Placebo Alone Eligibility Criteria Males or females ≥ 40 and ≤ 64 years of age BCDVA of 0.0 LogMAR(20/20 Snellen equivalent) or better in each eye under photopic conditions DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse in photopic conditions in each eye & binocularly Phase 2 Enrollment Completed Feb to May 2021 – 150 Subjects Reported Topline Results End of 2Q21 Endpoints Primary: % of subjects with ≥ 3 lines of improvement in distance- corrected near visual acuity comparing Nyxol + LDP vs placebo alone at 1 hour Secondary: • % of subjects with ≥ 2 and ≥ 3 lines gained at time points from 30 min to 6 hours in photopic lighting comparing Nyxol + LDP vs placebo, Nyxol alone, and LDP alone ● % of subjects with > 3 lines of near vision gain with less than 5 letters of distance loss Pupil diameter at time points Safety and tolerability Clinical trial NCT #04675151. DCNVA = distance-corrected near visual acuity. BCDVA = best corrected distance visual acuity; *3-4 evenings; VEGA-1 Study Design Ocuphire PHARMA#81P 81 VEGA-1: Demographics and Baseline Characteristics Treatment and Placebo Arms were Balanced in the VEGA-1 Phase 2 Clinical Trial Age (years): Median (Range) Sex: Male n (%) Female n (%) Race: White n (%) Other* n (%) Dark Iris Color: n (%) Light Iris Color: n (%) Photopic DCNVA Mean Letters read- Binocular (Snellen Equiv.) 70 letters = 20/20 Photopic BCDVA Mean Letters read- Binocular (Snellen Equiv.) 55 letters = 20/20 Photopic Pupil Diameter Mean (mm) Mesopic Pupil Diameter Mean (mm) Placebo Alone N=43 52 (42-62) 15 (35%) 28 (65%) 37 (86%) 6 (14%) 18 (42%) 25 (58%) 46 (20/63) 62 (20/15) 4.3 5.1 Nyxol Alone N=30 54 (41-60) 7 (23%) 23 (77%) 26 (87%) 1 (3%) 12 (40%) 18 (60%) 45 (20/63) 61 (20/15) 4.5 5.0 LDP Alone N=31 52 (44-64) 13 (42%) 18 (58%) 28 (90%) 3 (10%) 12 (39%) 19 (61%) 48 (20/63) 60 (20/15) 4.3 5.0 Source: VEGA-1 TLR Table 14.1.2.2 Demographics and Baseline Characteristics (PP Population). Snellen Conversion Chart. Nyxol+LDP Combo N=43 53 (43-63) 5 (12%) 38 (88%) 40 (93%) 3 (7%) 18 (42%) 25.1 (58%) 46 (20/63) 61 (20/15) 4.3 5.1 Total N=147 53 (41-64) 40 (27%) 107 (73%) 131 (89%) 15 (11%) 60 (41%) 87 (59%) 46 (20/63) 61 (20/15) 4.3 5.1 Ocuphire PHARMA#82P 82 VEGA-1: Nyxol+LDP Met Primary & Secondary Endpoints 61% Patients with Nyxol+LDP had ≥ 15 Letter Near Gain with Fast Onset & Durable Responses Percent of Subjects (%) 70% 60% 50% 40% 30% 20% 10% 0% Percent of Subjects with ≥ 15 Letters Binocular Photopic DCNVA Improvement from Baseline Phase 2 Primary Endpoint p=0.09 33% 16% 0 Rapid onset of efficacy p<0.0001 61% 14% VEGA-1 Phase 2 Trial 0.5 p=0.003 61% 28% 1 p<0.0001 63% Placebo (n=43) 16% 2 Time (Hours) p=0.02 47% 21% Nyxol+LDP (n=43) 3 p=0.02 21% 4 47% Durable benefit over 6 hours p=0.06 37% 19% Note: PP population differs from mITT by only one subject; results were essentially identical. Source: VEGA-1 TLR Table 14.2.1.2 Percent of Subjects with Improvement From Baseline in Photopic DCNVA by Time Point (PP Population). 15 letters is 3 lines. 6 Ocuphire PHARMA#83P 83 VEGA-1: Planned P3 Efficacy Endpoint Met by Nyxol+LDP Pre-Specified Endpoints Demonstrate Superiority of Combo vs. Components & ≥10 Letter Near Gain Percent of Subjects (%) 70% 60% 50% 40% 30% 20% 10% 0% ≥ 15 Letter Gain In Near & < 5 Letter Loss In Distance at 30 Minutes p=0.015 14% 61% VEGA-1 Phase 2 Trial Nyxol + LDP combination achieved statistical superiority to LDP and Nyxol alone arms even with a small sample size p=0.03 33% Placebo (n=43) Nyxol+LDP (n=43) Nyxol (n=30) p=0.008 26% LDP (n=31) 77% of subjects achieved > 10 letter improvement in DCNVA at 30 minutes (p=0.015 vs placebo) and similar trend at other timepoints Source: VEGA-1 TLR Table 14.2.2.2 Percent of Subjects with >= 15 Letters of Improvement in Photopic DCNVA and < 5 Letters of Loss in Photopic Binocular BCDVA by Time Point (PP Population); Table 14.2.1.2 Percent of Subjects With Improvement From Baseline in Photopic DCNVA by Time Point (PP Population) Ocuphire PHARMA#84P 84 VEGA-1: Improvement in Functional Near Vision Nyxol+LDP had a Rapid Improvement in Near Vision to 20/32 for many Patients Percent of Subjects (%) 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% 0% 7% 20/15 0% Binocular Photopic DCNVA Nyxol + LDP Improvement in Snellen Equivalent 84% 20/40 or Better Near Vision 68% 20/32 or Better Near Vision 12% 20/20 0% 23% 20/25 0% 26% 20/32 VEGA-1 Phase 2 Trial 0% Baseline 16% 20/40 33% 20/50 Snellen Acuity 11-Hour 40% 7% 20/63 $23% 0% 20/80 Source: VEGA-1 TLR Table 14.2.24.1 Percent of Subjects with Photopic DCNVA by Time Point (PP Population) 2% 0% 20/100 Visual Acuity Chart KCRHN ZKDV C HVORK RHSON KSVRH HNK CD NDVKO DHOSZ 20/32 VRNDO CZHKS 20/63 Ocuphire PHARMA#85P 85 VEGA-1: Mean Pupil Diameter Over Time Achieved Optimal Pupil Size in Nyxol+LDP (& Nyxol) Consistent with 3-line Near Vision Gain Mean Pupil Diameter (mm) 5 4 1 4.5 4.5 +4 4.5 4.4 Daily Evening Nyxol Dosing 12 hr minimum interval to Time 0 Baseline *** ***4.5 4.3 3.2 3.1 0 *** T 4.5 *** 3.2 HH 3.0 2.4 *** *** ** 1 Placebo (n=43) 4.4 3.2 2.5 2.1 VEGA-1 Phase 2 Trial Best Eye (PP Population) Mean Photopic Pupil Diameter *** *** ** 2 4.3 3.4 2.7 2.3 Time (Hours) *** -Nyxol+LDP (n=43) *** 4.4 3.3 *** 3.1 Nyxol+LDP arm statistically significant compared to all arms 3 2.5 -Nyxol (n=30) *** HH *** I *** 4 4.4 3.3 3.3 2.7 Placebo + LDP (n=31) Source: VEGA-1 TLR Table 14.2.12.1 Observed Values and Change from Baseline in Photopic Pupil Diameter by Time Point (PP Population) LO **p<0.01 ***p<0.0001 5 3.3 Both components maintained dynamic pupillary response *** 3.6 *** 2.9 4.6 6 Ocuphire PHARMA#86P 86 VEGA-1: Photopic and Mesopic Distance Vision Effects Nyxol and/or LDP Demonstrated No Loss of Distance Vision in Photopic and Mesopic Lighting Percent of Subjects (%) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Percent of Subjects With Improvement or Loss From Baseline in Photopic BCDVA at 1 hour 9% 28% 20% 19% 91% 72% 77% 74% VEGA-1 Phase 2 Trial Greater than or Equal to 5 Letter Gain Placebo (n=43) Nyxol+LDP (n=43) ■Nyxol (n=30) Within 5 Letters No Loss of Distance Vision 0% 0% 3% LDP (n=31) 7% Greater than or Equal to 5 Letter Loss Percent of Subjects (%) Percent of Subjects With Improvement or Loss From Baseline in Mesopic BCDVA at 1 Hour 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 9% 23% 27% 39% Greater than or Equal to 5 Letter Gain Placebo (n=43) 84% 72% 73% 55% Within 5 Letters No Loss of Distance Vision Source: VEGA-1 TLR Table 14.2.8.1 and 14.2.10.1 Percent of Subjects With Improvement or Loss From Baseline in Photopic and Mesopic BCDVA by Time Point (PP) Nyxol+LDP (n=43) Nyxol (n=30) 7% 5% 0% 7% Greater than or Equal to 5 Letter Loss LDP (n=31) Ocuphire PHARMA#87P 87 VEGA-1: Safety Findings Across All Arms Nyxol+LDP Combination (& Nyxol Alone) was Well Tolerated with a Favorable Safety Profile Total Treatment Emergent Adverse Events (n) TEAES by Severity (n [%]) Mild Moderate Severe AEs Occurring in ≥ 5% of subjects (n [%]) Instillation Site Pain (Mild) Instillation Site Erythema (Mild) Conjunctival Hyperemia (Mild) Eye Disorders (Mild) Placebo Alone Nyxol Alone n=45 n=30 4 1 (2.2%) 1 (2.2%) 0 (0%) 1 (2.2%) 0 (0%) 0 (0%) 1 (2.2%) Conjunctival Hyperemia CCLRU Scale for Reference 18 6 (20%) 0 (0%) 0 (0%) 3 (10%) 3 (10%) 2 (6.7%) 2 (6.7%) None 0) Mild (+1) Nyxol + LDP and LDP alone Only transient 0.5 point mean increase LDP Alone n=31 13 6 (19.4%) 0 (0%) 0 (0%) 0 (0%) 2 (6.5%) 0 (0%) 4 (12.9%) Moderate (+2) Nyxol+LDP n=44 50 13 (29.5%) 1 (2.3%) 1 (2.3%) 4 (9.1%) 5 (11.4%) 2 (4.5%) 5 (11.4%) Severe (+3) Source: VEGA-1 TLR Table 14.3.1.1 Overall Summary of Treatment Emergent Adverse Events (TEAE) (Safety Population) Table 14.3.1.3 Treatment-Emergent Adverse Events (TEAE) by System Organ Class, Preferred Term, and Severity (Safety Population) ● ● ● No deaths, no serious AEs Almost all AEs were mild 0% headaches or brow aches reported for Nyxol+LDP arm; headaches not reported in Nyxol trials ~5% mild, transient conjunctival hyperemia AEs in Nyxol+LDP arm Distance vision: 0% Nyxol + LDP arm had > 5 letter distance loss in photopic lighting (5% in mesopic) No change in IOP Ocuphire PHARMA#88P Efficacy Signal Percent of subjects with 23-line improvement in near vision with less than 5 letters of distance loss in Nyxol+LDP combo compared to Nyxol alone and LDP alone as demonstrated in well-controlled, multi-center clinical trials What's Important? Nyxol+LDP has the Potential to be "Best in Class" Presbyopia Eyedrop Safety No loss of distance (included in efficacy) Maintain night distance vision Well-tolerated Broad Label Opportunity For VuityTM, FDA did not limit the use of the product to clinical trial parameters such as: ● 88 age lighting conditions (photopic or mesopic) monocular or binocular phakic status Vuity Label 2021 FDA Guidance Physician/ Patients Efficacy Signal Achieve "functional near vision" and intermediate vision Achieve optimal pupil size Durability Dynamic/responsive pupil ● ● Safety No loss of distance vision No headaches or brow aches Reliable night distance vision No stinging or burning Minimal redness Patient Experience Tunability - ability to customize treatment based on patient's lifestyle needs Favorable tolerability for continued use and Rx refills Ocuphire PHARMA#89P 89 0.75% Nyxol Nyxol Alone in Presbyopia Presented by: James Katz, MD the Midwest O Center for Sight James Katz, MD University of Illinois, College of Medicine ● Ocuphire President of the Midwest Center for Sight Board-certified Ophthalmologist with specialties in Cornea, Cataract, and Refractive Surgery PHARMA Well-Published in Distinguished Ophthalmologic Journals With Over 50 Publications and Over 300 Presentations#90P VEGA-1 Study Design Assessed Nyxol Alone Efficacy Nyxol as Single Drop vs. Placebo Met Pre-Specified Endpoints in the Trial VEGA-1 Phase 2 Trial 17 US sites 150 Presbyopic patients 90 Visit 1 Screening/Baseline 0.75% Nyxol Nyxol or Placebo Placebo *3-4 daily evening doses and then visit 2 on Day 5 Source: VEGA-1 Study Design N=73 Nyxol (N=43) Nyxol (N=30) ~8PM Evening Dosing 4 days N=74 Placebo (N=31) Placebo (N=43) 12 Hrs LDP Drop 0 min No Treatment ~8AM Assessments for Nyxol Alone & Placebo LDP Drop No Treatment Visit 2 (Day 5) Nyxol + LDP (N=43) Primary Endpoint Nyxol (N=30) 30min 1 Hr 2 Hr 3 Hr 4 Hr 6 Hr Placebo (N=31) 18 Hrs Post-dose Placebo (N=43) ** Nyxol alone evaluated 12 hours post dosing Ocuphire PHARMA#9191 VEGA-1: Nyxol Meets Planned P3 Efficacy Endpoint at 12 Hours Nyxol as a Single Drop Provides a Statistical 3 Line or More Gain Compared to Placebo Percent of Subjects (%) 50% 40% 30% 20% 10% 0% VEGA-1 Phase 2 Trial Percent of Subjects with ≥ 15 Letters Binocular Photopic DCNVA Improvement from Baseline 12 Hours Post Nyxol Dose Placebo (n=74) Nyxol (n=73) 14% n=74 p=0.03 30% n=73 ≥15 Letters DCNVA Letters Gained (Time 0) Nyxol showed promising >15 letter near vision gain at 12 hours Source: VEGA-1 TLR Table 14.2.1.7 Percent of Subjects with Improvement in Photopic DCNVA at 0 Minutes for Nyxol and Placebo Treated Subjects (PP Population) Ocuphire PHARMA#92P 92 VEGA-1: >10 Letter Gain in DCNVA with Nyxol at 12 Hours Nyxol as a Single Drop Provides a Clinically Meaningful >10 Letter Gain Compared to Placebo Percent of Subjects (%) 70% 60% 50% 40% 30% 20% 10% 0% VEGA-1 Phase 2 Trial Percent of Subjects with ≥ 10 Letters Binocular Photopic DCNVA Improvement from Baseline Placebo (n=74) Nyxol (n=73) 28% n=74 p=0.005 53% n=73 > 10 Letters DCNVA Letters Gained at 12 Hours After Nyxol Dosing Nyxol showed promising ≥10 letter near vision gain at 12 hours Source: VEGA-1 TLR Table 14.2.1.7 Percent of Subjects with Improvement in Photopic DCNVA at 0 Minutes for Nyxol and Placebo Treated Subjects (PP Population) Ocuphire PHARMA#93P 93 VEGA-1: Improvement in Functional Near Vision Nyxol Single Drop Significantly Improves Functional Near Visual Acuity VEGA-1 Phase 2 Trial Percent of Subjects (%) 40% 35% 30% 25% 20% 15% 10% 5% 0% 0% 3% 20/15 Improvement in Snellen Equivalent 56% achieved 20/40 or better at 12 hours 0% 3% 12% 20/20 0% Binocular DCNVA Nyxol Alone 20/25 16% 0% 22% 20/32 0% 36% 20/40 Snellen Acuity Baseline 12 Hours Baseline Inclusion: Photopic DCNVA of 20/50 or worse 23% 34% Source: VEGA-1 TLR Table 14.2.24.1 Percent of Subjects with Photopic DCNVA by Time Point (PP Population) 15% 19% 5% 20/50 20/63 20/80 11% 0% 20/100 Nyxol achieved 20/40 vision at 12 Hours Ocuphire PHARMA#94P VEGA-1: Functional Vision Durability Single Drop of Nyxol has Durable Response for 18 Hours 18 hours post Nyxol consistent efficacy with 12 hours 94 0.75% Nyxol Subjects achieving 3-line gain in photopic, binocular DCNVA (N=30) Time Point (Hrs post Nyxol dose) 12.5 18 Nyxol as a Single Drop 18 % of Subjects 33% 37% Subjects achieving 20/40 or better in photopic, N/A binocular DCNVA (N= 30) (compared to baseline) *Trend toward statistical significance even in smaller Nyxol arm from time 0 to time 6 hrs (n=30); larger sample size for all arms planned in Phase 3 program Statistics vs Placebo 60% p=0.07* p=0.11* VEGA-1 TLR Table 14.2.1.2 Percent of Subjects with Photopic DCNVA by Time Point (PP Population) and Table 14.2.24.1 Percent of Subjects with Photopic DCNVA by Time Point (PP Population) Ocuphire PHARMA#95P 95 你好 VEGA-1 (Post-Hoc): Efficacy Across Presbyopia Ages Nyxol Highest Efficacy in Young Presbyopes as Expected; Also Efficacy Seen in Older Presbyopes Percent of Subjects (%) VEGA-1 Phase 2 Trial Percent of Subjects With 15 Letter Improvement From Baseline in Photopic DCNVA at 0 Minutes for Nyxol and Placebo Treated Subjects by Age Group 40-54 yrs and 55-64 yrs 40% 35% 30% 25% 20% 15% 10% 5% 0% Placebo Nyxol 20% n=48 Age 40-54 36% n=42 Age Groups 0% n=26 p<0.05 Age 55-64 Note: Trend toward statistical significance p=0.15 in age 40-54; larger sample size for all arms planned in Phase 3 program Source: VEGA-1 TLR Table 14.2.1.7.1 & 14.2.1.7.2 Percent of Subjects with Improvement in Photopic DCNVA by Age Group (PP Population) 23% n=31 Nyxol demonstrated efficacy in 55 to 64 age group and Efficacy seen at 12 hours Ocuphire PHARMA#96P 96 0.4% Ocuphire PHARMA Presbyopia Drops: Ocuphire Next Steps and Competitive Landscape Presented by: Jay Pepose, MD, PhD#97P 97 Two Treatment Options for Spectrum of Presbyopic Patients Two NDA Submissions Targeted in 2023: Nyxol Alone and Nyxol+LDP Pursuing Product Labels for 1 Drop and 2 Drop Options for the Treatment of Presbyopia Nyxol as a Single Agent for Presbyopia Single Durable Drop F Nyxol with LDP as Adjunctive Therapy for Presbyopia Two Drops Tunable Option Initiating VEGA Phase 3 Program in Mid-2022 for Both Labels Ocuphire PHARMA#98P 98 Potential 'Best in Class' Presbyopia Drop(s) Nyxol and Nyxol+LDP Combination Data Differentiates on Efficacy, Safety, and Durability Product Attributes* 1) Efficacy (3 Line Gain in DCNVA - Primary Endpoint Responders)* 2) Safety: Loss of Distance in Mesopic 3) Tolerability: Headaches and Conjunctival Hyperemia 4) Durability (% responders at the longest timepoint) VUITY™ 26-31% (3 hours) No Significant Loss >5% Headaches >5% redness 18% at 6 hours Caveats of cross- trial comparisons for VUITYTM and Nyxol/LDP. Differences include age, severity of near vision loss, lighting conditions, doses, timing, and # of patients Nyxol 30% (12 hours) Ocuphire No Significant Loss No Headaches >5% mild redness 37% at 18 hours Placebo Adjusted Values for Vuity were 15-23% in Gemini1 & 2; Placebo Adjusted Nyxol was 16% and Nyxol+LDP was 33% (all stat significant) Source: Nyxol Data: ASCRS (July 2021) Abstract# 76645 (Phase 2) and VEGA-1; Abstract 74336 (Phase 3). VUITYTM Data FDA Label and AAO 2021 Presentation. Nyxol+LDP ~61% (1 hour) No Significant Loss No Headaches ~5% mild redness 37% at 6 hours Nyxol's Potential Differentiated Solution Ocuphire PHARMA#99Presbyopia Eye Drops Competitive Landscape Validation of Pupil Modulating Drops Achieving Pin-Hole Effect & Efficacy, Many with Pilocarpine Other Cholinergic Agonists* 99 Pupil modulation MOA Soften lens MOA Combination drugs *act on sphincter and ciliary muscles in dose- dependent manner Cholinergic Agonist* (pilocarpine) Visus Lenz (PRX-100; (BrimocholⓇ; brimonidine + aceclidine) carbachol) Eyenovia (MicroLine; 2% pilo) Allergan (VUITY™M; 1.25% pilo) NDA Orasis (CSF-1; Low dose pilo) Phase 3 Phase 2 Phase 1 Novartis (EV-06) Ocuphire (0.75% Nyxol) Alpha-1 Antagonist Nyxol is differentiated as a new MOA class using the iris dilator muscle to reach an optimal pupil size Ocuphire (0.75% Nyxol +0.4% pilo) Alpha Antagonist & pilocarpine* Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020 Ocuphire PHARMA#100P 100 Large and Growing Presbyopia Market Presented by: James Katz, MD Ocuphire PHARMA#101P 101 Presbyopia is a Burgeoning Opportunity One of the Largest Disease Segments, Increasing Spend from Global Reading Glasses Market ● The Problem • Lens loses ability to change shape when viewing objects up close as we age Dependence on reading glasses for intermittent and prolonged use, but unable to see near and far at same time Aesthetics and inconvenience 100% of adults over the age of 40 years are at risk of developing presbyopia Presbyopes (US) ~128 M Global Reading Glasses Market (USD Billion), 2019 & 2027 Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, Cataract & Refractive Surgery Today, 2021, NEI 2010 data. Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday. NEI/NIH https://www.nei.nih.gov/sites/default/files/health-pdfs/Presbyopia.pdf $36 B 2019 $56 B 2027 Ocuphire PHARMA#102P Key Findings from GlobalData Market Research on Presbyopia Insights Very Consistent with Other Competitors Market Research Surveys 120+ Million Presbyopia patients in the US 51% physicians would offer eye drops as a first-line presbyopia treatment 102 90% presbyopia patients wear reading glasses ≥ once per day Physician Perspective N=120 Global Data Market Research Survey 67% physicians indicated interest in Nyxol+LDP 70% patients would consider an eye drop as an alternative to reading glasses 70% patients considered the 2 drops/bottle dosing to be moderately-to-very convenient 40% patients have asked their physicians about alternatives to reading glasses ≥ $50/mo Patient Willing to Pay Vuity ™M is priced at $79 for a 30-day supply Patient Perspective n-=134 Ocuphire PHARMA#103P 103 Presbyopia Market Segments Tens of Millions of Likely Early Users → Emmetropes, Hyperopes, and Pseudophakes ~128M Presbyopes in the US ● NORMAL VISION Emmetropes Naturally occurring clear vision • No refractive error/post-LASIK 66 M HYPEROPIA Hyperopes Poor near vision (starting at age 40) 14 M PSUEDOPHAKIA Pseudophakes • Cataract surgery for artificial lens (monofocal, multifocal IOLS) 9 M Assume 50% use eye drops* ~44 M Patients Likely To Be Early Users of Presbyopia Eyedrops Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, NEI 2010 data. *GlobalData Market Research 2020 Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday. MYOPIA Myopes Poor distance vision 39 M Ocuphire PHARMA#104P VuityTM is the First FDA-Approved Eyedrop for Presbyopia Approval Sets the Stage for Market Development by Large Pharma to Build a Large Market FDA Approval of VuityTM positive for the presbyopia space Opportunities for new entrants with differentiated product attributes in a newly established segment with physicians and patients/consumers 104 ~44 M Patients Likely To Be Early Users of Presbyopia Eyedrops 3-6 refills per year assumed Private Cash Pay (VuityTM fill List Price) Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, Cataract & Refractive Surgery Today, 2021, NEI 2010 data. Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday. -$10B - $20B Estimated US Presbyopia Market Opportunity ~2 Billion Presbyopes Globally for Even Larger Market Potential Ocuphire PHARMA#105105 P NyxolⓇ for PRESBYOPIA QUESTION & ANSWER#106P 106 Summary of Nyxol and Nyxol+LDP Presbyopia Program 慢 Г J Nyxol as a single drop is differentiated as a new MOA class working on the iris dilator muscles; Nyxol with LDP as adjunct therapy uniquely offers pupil 'tunability' depending on patient lifestyle In VEGA-1 trial: Nyxol+LDP met its primary efficacy endpoint ≥ 15 letter near visual acuity gain. Nyxol as a single drop met efficacy endpoints at 12 hours and 18 hours Consistent with prior trials across other indications, Nyxol, dosed alone or with LDP, has demonstrated favorable safety and tolerability VEGA Phase 3 program planned for Nyxol and Nyxol+LDP for the treatment of presbyopia to initiate mid-2022 Potential NDA submissions for presbyopia in 2023 Nyxol as a single drop Nyxol with LDP as adjunct therapy Presbyopia drops projected to be one of the largest $10+B new segments in Ophthalmology Ocuphire PHARMA#107107 Closing Remarks Mina Sooch, CEO, Founder of Ocuphire Pharma Ocuphire PHARMA#108108 Ocuphire Management Team Decades of Biotech and Drug Development Experience POINT GUARD PARTNERS LLC Ronil Patel, MS Senior Director BD and Market Strategy FLORIDA TECH BETALIO Revitalid MERCK Bindu Manne Head, Market Development and Commercialization 'UNC PEMBROKI Ocularis Pharma Prudential Syber Goldman DevBx Sachs OCULOS Integrated Insight. Therapeutix" 1 ThromboGenics® Charlie Hoffmann, MBA VP Corporate Development and Operations Takeda Shire Tuck School of Business IIIII at Dartmouth 1900 equinox Daniela Oniciu, PhD Global Head, R&D, Chemistry and Product Development UNIVERSITY of UF Gemphire ESPERION Cerenis™ Pfizer THERAPEUTICS aerpio Gemphire Therapeutics MONITOR ProNAI Chris Ernst Global Head, QA and Manufacturing NORTHERN KENTUCKY UNIVERSITY Akebia THERAPEUTICS VE DI ES MEDPACE Mina Sooch, MBA President & CEO and Founder HARVARD BUSINESS SCHOOL Apjohn Ventures MIMICHIGAN ROSS Pfizer Gemphire Therapeutics NeuroBo PHARMACEUTICALS Mitch Brigell, PhD Head, Clinical Development and Strategy KANSAS STATE aerpio & NOVARTIS Amy Rabourn, CPA VP, Finance UNIVERSITY Pfizer Laura Gambino Director, Project Management EASTERN MICHIGAN UNIVERSITY aerpio Akebia Pfizer THERAPEUTICS pwc Barbara Withers, PhD VP, Clinical and Regulatory Strategy SIRION Therapeutics WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE GE aerpio GUBC Pfizer Drey Coleman VP, Clinical Operations OCULOS Integrated Insight. UCF Ocuphire PHARMA#109109 Ocuphire's World-Class Medical Advisory Board Fortunate for the Insights of Leading KOLS & Drug Candidate Co-Founders PeposeVision INSTITUTE Refractive Specialist Jay Pepose, MD, PhD UCLA School of Medicine the Midwest Center for Sight Refractive Specialist James Katz, MD University of Illinois Jacksoneye seeing beyond your imagination Refractive Specialist Mitch Jackson, MD University of Chicago MINNESOTA EYE CONSULTANTS Refractive Specialist Thomas Samuelson, MD University of Minnesota CEI CINCINNATI EYE INSTITUTE Refractive Specialist Ed Holland, MD Loyola University Chicago OCLI Setting The Standard In Eye Care Refractive Specialist Marguerite McDonald, MD Columbia University Chu Vision INSTITUTE Refractive Specialist Y. Ralph Chu, MD Northwestern University arcscan Imaging ahead of the curve Refractive Specialist Jack Holladay, MD University of Texas KENTUCKY EYE INSTITUTE Optometry Paul Karpecki, OD Indiana University elCON Medical Refractive Specialist Eliot Lazar, MD Georgetown University INDIANA UNIVERSITY MELVIN AND BREN SIMON CANCER CENTER Ų Mark Kelley, PhD Indiana University Co-Founder Apexian/APX3330 NEW ENGLAND RETINA CONSULTANTS Retinal Specialist David Lally, MD Vanderbilt University Duke Eye Center Retinal Specialist Michael Allingham, MD, PhD University of North Carolina EYE CARE ASSOCIATES OF NEVADA Optometry Douglas Devries, OD University of Nevada Cleveland Clinic Cole Eye Institute Retinal Specialist Peter Kaiser, MD Harvard Medical School Retina-Vitreous Associates Medical Group Retinal Specialist David Boyer, MD Chicago Medical School RETINA CONSULTANTS OF AMERICA Retinal Specialist David Brown, MD Baylor University OPHTHALMIC CONSULTANTS OF BOSTON EXCELLENCE IN EYE CARE Retinal Specialist Jeffrey Heier, MD Boston University Ocuphire PHARMA#110110 Ocuphire Board of Directors Seasoned Directors with Decades of Drug Development, M&A/Financings, & Ophthalmology Cam Gallagher, MBA Chair, Board Director University of San Diego A VELOSBIO ONCTERNAL therapeutics zentalis RetroSense THERAPEUTICS Mina Sooch, MBA Vice-Chair, Board Director President & CEO HARVARD BUSINESS SCHOOL Gemphire Therapeutics MONITOR ProNAI Apjohn Ventures James Manuso, PhD/MBA Board Director Columbia Business School astex pharmaceuticals Talfinium Investments, Inc. GALENICA PARTNER IN PHARMACEUTICAL TECHNOLOGY Sean Ainsworth, MBA Lead Independent Director, Board Director Washington University in St. Louis OLIN BUSINESS SCHOOL Allergan RetroSense THERAPEUTICS Richard Rodgers, MBA Board Director CARLSON IMMUSOFT Programming Cures SCHOOL OF MANAGEMENT UNIVERSITY OF MINNESOTA TESARO™ MGI. PHARMA CA BioScience Jay Pepose, MD, PhD Board Director SOLO UCLA Théa let's open our eyes PeposeVision INSTITUTE Wilmer Eye Institute David Geffen School of Medicine Washington University in St. Louis Susan Benton, MBA Board Director USF MUMA COLLEGE OF BUSINESS UNIVERSITY OF SOUTH FLORIDA BAUSCH + LOMB Shire Ocuphire PHARMA#111111 Thanks To Our Network of Partners A Strong Foundation has been Built to Efficiently Grow and Deliver Our Vision for Patients... 5+ Reg/Preclin Consultants Refractive Patients 4+ Stats/Labs 2 Pre-Clin/Tox CROS 50+ Clinical Investigators 2 Clinical CROS 10+ Patent/Profess. Advisors OCUPHIRE Team (15+) 4+ CMC Consultants 5 MD Interns 18 Medical Advisors 3 Global API Mfrs 6+ Final Product/ Packaging Mfr Retina Patients Ocuphire PHARMA#112JJ 는 112 Track Record of Achieving Milestones ➜ Exciting 2022 News Cadence → Multiple Late-Stage Data Catalysts Expected in 2022 for Potential First NDA Approval in 2023 2021 Report Positive Phase 3 Data for RM (MIRA-2) Report Positive Nyxol+LDP Phase 2 Data for Presbyopia (VEGA-1) New Patent Claims for Presbyopia ASCRS 2021 Presentation for MIRA-2 & VEGA-1 Manufacture 3xRegistration Batches for Nyxol Blow-Fill- Seal (BFS) Eye Drops Initiate 2nd Phase 3 RM AND Pediatric RM trial 2022 Report Positive Nyxol Alone Phase 2 Data for Presbyopia Report 2nd Phase 3 Data for RM (MIRA-3) Report Pediatric Data in RM (MIRA-4) Report Phase 3 Data for NVD (LYNX-1) Submit Nyxol NDA for RM Report Phase 2 Data for DR/DME (ZETA-1) Initiate VEGA Phase 3 Presbyopia Progam Ongoing Partnering Discussions with Leading Ophthalmic Companies (including European and Asian Players) Early 2022 Ocuphire PHARMA#113G 113 Overall Highlights from Ocuphire Investor R&D Day NyxolⓇ Nyxol® eye drops, as a platform, is uniquely positioned to address growing markets in refractive disorders Nyxol, if approved in 2023, would be the only Rx drop for reversing dilations and positively impact the patient experience in an eye care practice Nyxol represents a novel class with a differentiated MOA and potential as a convenient single evening drop with efficacy at 12 hours (and 18 hours) in the large presbyopia market Ocuphire plans to pursue both Nyxol as a single agent and with low dose pilocarpine as adjunctive therapy to treat a breadth of presbyopia patient types → more details to follow APX3330 The well-controlled, multi-center Phase 2b ZETA-1 for APX3330 is ~70% enrolled APX3330 new interim masked safety data support favorable safety profile as a potential oral treatment for diabetics with DR/DME APX3330 oral with dual MOA targeting VEGF and inflammation may be well-suited to reduce treatment burden and/or improve outcomes adjunctive to traditional anti-VEGF intravitreal injections across retinal diseases ** Ocuphire PHARMA#114114 Ocuphire Restore Vision & Clarity Thank You for Joining Us Click Here for the Recorded Event Ocuphire Pharma Investor R&D Day January 31, 2022