Form: 8-K

Current report filing

August 1, 2023

Documents

Exhibit 99.1

 Restore Vision & Clarity  Ocuphire Corporate Presentation  August 2023 
 
 2  This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements concerning the success and timing of planned regulatory filings and approvals, pre-commercial activities, commercialization strategy and timelines, business strategy, product labels, cash runway, scalability, future clinical trials in presbyopia (P), dim light/night vision disturbance (DLD) and diabetic retinopathy (DR) / diabetic macular edema (DME), including the potential for Nyxol to be a “best in class” presbyopia drop, and timing of planned future clinical trials for APX3330, APX2009 and APX2014, timing and occurrence of an End-of-Phase 2 meeting with the FDA, the potential of a Phase 3 registration path for APX3330, the success and timing of planned regulatory filings, business strategy, cash runway, scalability, the potential for APX3330 to be the most advanced and the first line of therapy for DR patients, and the potential market opportunity for the slowing of DR progression. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success, costs, and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; (ii) regulatory requirements or developments; (iii) changes to clinical trial designs and regulatory pathways; (iv) changes in capital resource requirements; (v) risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vi) legislative, regulatory, political and economic developments, (vii) changes in market opportunities, (viii) risks that the partnership with Viatris may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates; (ix) the success and timing of commercialization of any of Ocuphire’s product candidates, including the scalability of Ocuphire’s product candidates and (x) the maintenance of Ocuphire’s intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and may be filed by the Company from time to time with the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.  The Company makes no representation or warranty, express or implied, as to the accuracy or completeness of the information contained in or incorporated by reference into this presentation. Nothing contained in or incorporated by reference into this presentation is, or shall be relied upon as, a promise or representation by the Company as to the past or future. The Company assumes no responsibility for the accuracy or completeness of any such information. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.  Disclosures and Forward-Looking Statements 
 
 3  Corporate Highlights  Strong Financial Position to Advance APX3330  Late-Stage Clinical Candidates for Retinal Diseases Represent Multi-Billion Dollar Opportunity  APX3330: Paradigm Changing, Non-invasive, Safe Oral Tablet for millions of NPDR patients that are currently left untreated  Ref-1, a novel, dual target (angiogenesis and inflammation) for retinal diseases  ZETA-1 Phase 2 demonstrated slowing progression of Diabetic Retinopathy (DR) with statistically significant efficacy on potential Phase 3 registration endpoint  Nyxol: Eyedrops for refractive disorders  Global License Agreement with Viatris to Fund all Development and Commercialization for Nyxol Indications:  Reversal of Mydriasis (RM)- PDUFA Date on September 28, 2023. Approval would trigger $10M milestone  Presbyopia- currently in Phase 3  Dim Light Disturbances- currently in Phase 3 
 
 4  Ocuphire Pipeline  Product Candidate  Indication  Pre-clinical  Phase 1  Phase 2  Phase 3  Regulatory Approval  Upcoming Milestones  APX3330  Oral Pill  Diabetic Retinopathy (DR)  EOP2  Meeting  EOP2 Mtg Q4 2023  APX3330  Local Delivery  Retina  Select retinal drug delivery technology  APX2009 and APX2014  Local Delivery  Retina  Select retinal drug delivery technology  Nyxol® Eyedrops  Reversal of Mydriasis (RM)  Partnered with Viatris  PDUFA Date Sep 28, 2023  Presbyopia (P)  VEGA-2 Phase 3 Topline Data Q4 2023  Dim Light or Night Vision  Disturbances (DLD)  LYNX-2 2nd Phase 3 trial (n=150+) 
 
 5  Diabetic Retinopathy Market and Unmet Need 
 
 6  Diabetic Eye Disease is Common Cause of Blindness  Diabetes and Diabetic Retinopathy (DR)  https://webeye.ophth.uiowa.edu/eyeforum/tutorials/diabetic-retinopathy-med-students/Classification.htm  https://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011  https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193  Diabetes Mellitus is a group of diseases characterized by high blood glucose levels. Diabetes results from defects in the body's ability to produce and/or use insulin  Diabetic retinopathy (DR) occurs when fluctuations or instability in blood glucose levels damages blood vessels in the retina  Type 1 diabetes (T1D): The body produces very little or no insulin, which means that patients need daily insulin injections to maintain blood glucose levels  Type 2 diabetes (T2D): The most common form of diabetes - either the body does not produce enough insulin, or resists insulin  Normal Retina Diabetic Retina  Two Types of DR  Non-Proliferative Diabetic Retinopathy (NPDR) – most common form of DR – early stages of edema and exudates, blurred central vision  Proliferative Diabetic Retinopathy (PDR) – later stage of DR, marked by abnormal blood vessels and scar tissue on retina  Diabetic Macular Edema (DME) can occur at any stage of DR 
 
 7  American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions;  Das UN. DME, retinopathy and age-related macular degeneration as inflammatory conditions. Arch Med Sci. 2016;12(5):1142-1157. doi:10.5114/aoms.2016.61918  Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000  Guidehouse Triangulation of Global Data, Market Scope and Investor Forecasts (2020) AMD = Age-Related Macular Degeneration; DME = Diabetic Macular Edema ; BRVO = Branch Retinal Vein Occlusion  National Center for Chronic Disease Prevention & Health Promotion. Health & economic costs of chronic diseases. Atlanta (GA): Centers for Disease Control & Prevention, US Department of Health and Human Services; 2018  Four-Year Visual Outcomes in a Randomized Trial of Intravitreous Aflibercept for Prevention of Vision Threatening Complications of Diabetic Retinopathy (Protocol W).” JAMA. February 7, 2023  Diabetic Retinopathy At a Glance  Current Treatment Landscape Demonstrates Need for Non Invasive Therapies  The number of people with DR expected to increase more than 14M by 2050  There are ~8M adults in the U.S. with NPDR  DR is the leading cause  of blindness among working- age adults with the median age of onset at 45 – 50 years  Majority of moderate to severe patients with DR are not treated with anti-VEGF due to injection burden and no benefit to visual acuity  Prevention of Progression is favored by payors in chronic disease such as diabetes which is the leading cost driver  Physicians have no non-invasive options for NPDR with current standard being wait-and-monitor 
 
 8  American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions; Spherix Global Insights  Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000  Estimates are provided by the National Eye Institute, FactSheet, Global Data, and Research and Markets. Estimated values are rounded.  Estimated prevalence in the U.S.; DME- Diabetic Macular Edema; Age-related Macular Degeneration; Geographic Atrophy; Retinal Vein Occlusion  U.S Diabetic Retinopathy Market  10M Diabetic Retinopathy (DR)  8M  NPDR Patients  US Market Opportunity  Target Patient Population  ~$6B+  27%  27%  24%  22%  Proliferative diabetic retinopathy (PDR)  Severe non-proliferative diabetic retinopathy  (NPDR)  Moderate non-proliferative diabetic retinopathy (NPDR)  Mild non-proliferative diabetic retinopathy  (NPDR)  78% NPDR  Non-Proliferative DR  Proliferative DR  Majority of the DR patients are NPDR Severity  Target Population for APX3330  Real-World Chart Review of DR Patients in US  % of Patients  34 Million Diabetics in US  Types of DR 
 
 9  Spherix Global Insights: DR Market DYNAMIX October 2022  Early treatment diabetic retinopathy study research group. ophthalmology. 1991;98(5 suppl):823-33.  Diabetes control and complications trial research group. N Engl J Med. 1993;329(14):997-86.  Fathy C, Patel S, Sternberg P Jr, Kohanim S. Disparities in adherence to screening guidelines for diabetic retinopathy in the United States: a comprehensive review and guide for future directions. Semin Ophthalmol. 2016;31(4):364–377. doi: 10.3109/08820538.2016.1154170  Progression Based on DR Severity  NPDR Patients are Rarely Treated with anti-VEGF Intravitreal Injections; Non-Invasive, Early Intervention is an Unmet Need  0%  20%  40%  60%  80%  100%  Mild NPDR (35)  Moderate NPDR (43)  Moderately Severe NPDR (47)  Severe NPDR (53)  5%  12%  26%  52%  14%  30%  48%  71%  25%  40%  66%  80%  1 Year Follow-up     5 Year Follow-up  3 Year Follow-up  Percentage of Eyes that Worsen to PDR  Regardless of severity, all eyes worsen over time 
 
 10  10%  20%  30%  40%  50%  60%  70%  International US  59.5%  60.5%  17.0%  24.9%  7.7%  7.8%  4.9%  3.1%  10.9%  3.7%  ASRS 2021 Preferences and Trends (PAT) Survey  ASRS PAT Survey: Majority of Physicians Use a “Wait and Monitor” Approach for DR  NPDR Patients Are Not Treated Proactively and Anti-VEGF Use is Limited  How do physicians treat patients with severe NPDR without DME?  Closely monitor retinopathy and encourage  systemic glycemic control  Consider anti-VEGF in some patients with poor glycemic control and/or other risks  Consider anti-VEGF in some patients with good  glycemic control and compliance  Consider anti-VEGF therapy in all or  most patients  Other 0% 
 
 11  Diabetic Retinopathy Treatment Landscape 
 
 12  Landscape of Non-Invasive Therapies for Diabetic Retinopathy  Ocuphire’s APX3330 is the Most Advanced and The Only Dual Mechanism Oral Drug Candidate  Company websites and www.clinicaltrials.gov (as of July 31, 2023)  ✓  Completed  ◌  Ongoing  ✕  Discontinued  Company  Drug  Target/MOA  Indication  Route of Administration  Phase 1  Phase 2  Phase 3  Primary Endpoint/ Secondary Endpoints  APX3330  Ref-1 inhibitor  (Anti-VEGF and Anti-inflammatory)  DR  Oral  ✓  ✓  2022  2020: 2-step DRSS @wk24  RG7774  CB2 receptor (cannabinoid)  DR  Oral  ✓  ◌  2020: 2-step DRSS @wk36  BAY1101042  Guanylate Cyclase activator  DR  Oral  ✓  ◌  2021: 2-step DRSS @wk24  OPL-0401  ROCK 1/2 inhibitor  DR  Oral  ✓  ◌  2021: 2-step DRSS @wk24  OTT166  Integrin inhibitor  DR  Eyedrop  ✓  ◌  2022: 2-step DRSS @wk24  Note: Two Tyrosine Kinase and a Plasma Kallikrein Inhibitors failed as orals in Phase 2 due to dose limiting adverse events (e.g., liver and cardiovascular)  APX3330 Differentiation  Mechanism: Dual MOA targeting validated retinal pathways of angiogenesis and inflammation  Human exposure: >10,000 subject days of systemic exposure in humans at 600mg/day dose  Favorable safety and tolerability 
 
 13  Landscape of Invasive Therapies (IVT/Suprachoroidal) for Diabetic Retinopathy  Eylea®/Lucentis® Approved, But Not Used in Patients with NPDR; Rarely Used in Mild PDR  Company  Drug  Target/MOA  Route of Administration  Phase 1  Phase 2  Phase 3  Commercial  Eylea® (aflibercept)  VEGF-A/B; PIGF  Intravitreal  ✓  ✓  ✓  *1  Lucentis® (ranibizumab)  VEGF-A  Intravitreal  ✓  ✓  ✓  *2  KSI-301  (Tarcocimab)  VEGF  Intravitreal  ✓  N/A  ◌  EYP-1901  Voloronib* (TKI)  Intravitreal  ✓  ◌  BI 764524  Anti-Sema3A Ischemia modulator  Intravitreal  ✓  ◌  OTX-TKI  Axitinib* (TKI)  Intravitreal  ✓  ◌  RGX-314  AAV8-VEGF  Suprachoroidal (Gene Therapy)  ✓  ✓  Completed  ◌ Ongoing X Discontinued  *Trials to Support Approval  1 Panorama Clinical Trial  2 Protocol I & T and Rise & Ride  * Failed as oral/systemic treatments in retina due to dose limiting toxicity  Company websites and www.clinicaltrials.gov (as of July 31, 2023)  Eylea® is trademark of Regeneron and Lucentis® is trademark of Genentech 
 
 14  APX3330 Background 
 
 15  Logsdon et al (2018), Li et al (2014).  APX3330 History and Ref-1 Inhibition Mechanism  Ref-1 Involved in Key Pathways that Contribute to Diabetic Retinopathy and DME  Mechanism of Action – Ref-1 Inhibition  Hypoxia  Ref-1  HIF-1α  VEGF  (Signaling Cascade)  Inflammation  Ref-1  NF-κB  Other Growth Factors (Signaling Cascade)  TNF-α  Chemokines  Neovascularization  Lucentis® EYLEA®  Anti-VEGF  Steroids  APX3330  Ref-1 (reduction-oxidation effector factor-1), a novel target for retinal diseases, is a transcription factor regulator of angiogenesis (VEGF) and inflammation (NFkB)  Unique dual MOA decreases abnormal angiogenesis and inflammation  Anti-VEGF injections do not target inflammation  Previously developed by Eisai for hepatic inflammatory indications and by Apexian for solid tumors in 11 Phase 1 and 2 trials  Extensively studied in over 20 in-vitro and animal studies with favorable efficacy and safety 
 
 16  APX3330: Drug Development History and Patents  Significant Preclinical & Clinical Data Supporting Human Safety, MOA, and PK  12*  Phase 1 & Phase 2 Trials  Exposure in Humans  >10,000  Subject Days at 600mg/day  Patents to  2034+  Studied in inflammation/hepatitis & cancer patients  (Studied by Eisai & Apexian, respectively)  APX3330  New Chemical Entity  Preclinical Efficacy & Toxicology Package  APX3330 IND  6 Phase 1 Trials  5 Phase 2 Trials  Phase 2 Trials  Phase 3 Registration  NDA Filing  Focus on Ophthalmology  * Includes ZETA-1 trial 
 
 17  Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018  Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID: 21378315  Fehrenbacher, J. C., Guo, C., Kelley, M. R. & Vasko, M. R. DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA repair function of APE1. Neuroscience 366, 23-35, doi:10.1016/j.neuroscience.2017.09.039 (2017).  In-vitro Validation of Mechanism of Action  APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection  APX3330 reduces pro-inflammatory cytokines in LPS stimulated macrophages  Increasing APX3330 dose  VEGF  APX3330 reduces VEGF protein expression in preclinical stroke model  Control APX3330  APX3330 enhances Ref-1 endonuclease activity in dorsal root ganglion neurons  APX3330 increases DNA oxidative repair and neuronal protection 
 
 18  APX3330 VEGF Effects in Normal Cells  Abnormal Conditions (e.g., hypoxic):  Increased level of VEGF activity  Normal Conditions:  Physiological level of VEGF activity  Kamba 2007; Girardi 2010; Li 2014  APX3330 Investigator Brochure  Biologic anti-VEGF agents inactivate VEGF directly and reduce VEGF levels below normal levels  Inhibition of Ref-1 by APX3330 returns VEGF levels to normal levels  VEGF is a growth factor that is necessary for normal function of multiple cell types including vascular endothelium and neurons  By returning VEGF levels to normal, APX3330 can reduce neovascularization, vascular leakage and the inflammatory response without adverse systemic effects  The safety profile of APX3330 to date has not shown any of the adverse effects that has been seen with systemic administration of anti-VEGF biologics such as cardiovascular pathology, hypertension, arteriothrombotic events, or renal dysfunction  APX3330  ARPE-19 cell line  APX3330 prevents VEGF overproduction in ARPE-19 cells  APX3330 Restores Normal Levels Unlike Biologic Anti-VEGFs that Reduce VEGF Below Normal 
 
 19  APX3330 ZETA-1 Clinical Trial 
 
 20  ZETA-1: Phase 2 Trial of Oral AP3330 in Subjects With Diabetic Retinopathy  Multi-center, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial  Primary:  % subjects with ≥ 2 step improvement on DRSS (Diabetic Retinopathy Severity Scale1) at week 24  Secondary:  DRSS improvement ≥1, ≥2, ≥3, ≥4 study eye, fellow eye, binocular  DRSS worsening ≥1, ≥2, ≥3, ≥4, study eye, fellow eye, binocular  Progression to vision threatening complications  Central subfield thickness (CST)  Best Corrected Distance Visual Acuity (BCDVA)  DME fellow eye status  Safety and tolerability  Exploratory:  Inflammatory cytokines  Endpoints  25 US sites  N = 103 participants with moderately severe to severe NPDR or mild PDR (DRSS 47, 53, 61)  Key inclusion:  ≥ 18 years of age  DRSS 47, 53, or 61  Noncentral DME permitted2  ETDRS BCVA ≥ 60 letters (20/63)  Key exclusion:  OCT CST >320 µm2  Center involved DME allowed in fellow eye  Anti-VEGF within past 6 months3  HbA1c ≥ 12.0%  Eligibility Criteria  103 subjects enrolled (FPFV Apr 2021 to LPLV Aug 2022) Topline announced in January 2023  1:1  By Central Reading Center  Center-Involved DME in Fellow Eye is Acceptable  Includes Systemic or IVT VEGF  www.clinicaltrials.gov (NCT04692688); Eylea® is registered trademark of Regeneron NPDR = non-proliferative diabetic retinopathy PDR = proliferative diabetic retinopathy  Week 0  Week 12  Week 24  Week 4  Primary Endpoint  APX3330 600mg/day (BID)  Placebo BID  Randomization 
 
 21  ZETA-1: Baseline Demographics and Systemic Characteristics  Well-Balanced Across Arms  ZETA-1 Clinical Trial  APX3330 n=51  Placebo n=52  Age (years)  mean (range)  54.3  58.3  (26-81)  (24-78)  Sex: Male n (%)  24 (47%)  26 (50%)  Race: White n (%)  40 (78%)  41 (79%)  Ethnicity: Hispanic or  Latino n (%)  28 (55%)  23 (44%)  Diabetes Status (years)  mean (range)  15  (0-36)  16  (0-58)  Systolic Blood Pressure  (mmHg)  mean  136  139  Diastolic Blood Pressure  (mmHg)  mean  82  80  Heart Rate (beats/min)  mean  77  76  Hemoglobin A1C (%)  mean  8.4  8.3  Body Mass Index  (kg/m^2)  mean  31  31  DRSS Scores  APX3330 n=51  Placebo n=52  Total n=103  BCVA Study  Eye  Letters (mean)  81  78  80  (20/25  Snellen)  BCVA Fellow  Eye  Letters (mean)  76  77  77  (20/32  Snellen)  OCT CST  Study Eye  (µm)  270  271  271  OCT  CST Fellow  Eye (µm)  292  286  289  Intraretinal Fluid in the Center of SE  Y – 21  N – 26  Y – 12  N – 31  Y – 33  N – 57  Intraretinal Fluid at the Foveal Cente  r of SE  Y – 1  N – 20  Y – 1  N – 11  Y – 2  N – 31  Intraocular Pressure in Study Eye (mmHg)  15  16  15  APX3330 n=49  Placebo n=52  DRSS Score – Study Eye  47 (Moderately severe to severe  NPDR)  22 (43%)  18 (35%)  53 (Moderately severe to severe  NPDR)  25 (49%)  28 (54%)  61 (Mild proliferative diabetic  retinopathy)  4 (8%)  6 (12%)  DRSS Score – Fellow Eye  43 or Lower (Mild to moderate  NDPR or better)  15 (31%)  13 (25%)  47 (Moderately severe to severe  NPDR)  15 (31%)  20 (38%)  53 (Moderately severe to severe  NPDR)  12 (25%)  10 (19%)  61 (Mild proliferative diabetic  retinopathy)  1 (2%)  4 (8%)  65 or Higher (Moderate to  severe prolif. DR)  6 (12%)  5 (10%)  Demographics Key Visual Metrics  Good Visual Acuity Fluid Below 320µm  Note: 15 fellow eyes were CST>320 microns (center-involved DME eyes) 
 
 22  Percent of Subjects With ≥ 2-Step Improvement in DRSS From Baseline  ZETA-1 Did Not Meet the Week 24 Phase 2 Primary Endpoint (based on Anti-VEGF Precedence for DR)  30%  25%  20%  15%  10%  5%  0%  35%  Percent of Subjects (%)  (N=49)  (N=46)  p=0.98  p=0.27 4%  7% 8%  n=41 n=39  0%  n=48 n=47  Week 12 Visit  Week 24  Placebo (N=50) APX3330 (N=48)  ZETA-1 Clinical Trial  Note: Large “N” indicates total number of participants within each arm for the mITT population. Small “n” indicates total number of evaluable eyes for each respective endpoint and arm.  Percent of Subjects With ≥ 2-step Improvement in DRSS From Baseline by Visit  (mITT) – Study Eye 
 
 23  Clinically Meaningful Registration Endpoints in DR  Systemic Drugs Should Evaluate DRSS Change in Both Eyes; To Be Formally Confirmed at EOP2 FDA Meeting  10  81-85  71-75  Local Drugs (Intravitreal Injections) Systemic Drugs  Precedent approvable endpoint for locally- delivered drugs (Non-Systemic) in DR:  ≥ 2-step DRSS improvement in study eye  Aflibercept (PANORAMA trial)  Ranibizumab (RISE/RIDE/DRCR trials)  Potential approvable endpoints for systemic drug in DR (to be confirmed at the EOP2 FDA meeting) include:  ≥ 3-step binocular DRSS improvement  ≥ 3-step binocular DRSS worsening  End-of-Phase 2 meeting with FDA to align on binocular ≥ 3-step DRSS worsening (i.e., sum of right and left eye change in DRSS) as an acceptable primary endpoint for registration  This endpoint is distinct from historical anti-VEGF IVT precedent due to different delivery  Source: ZETA-1 Clinical trial  1. Nair P, Aiello LP, Gardner TW, Jampol LM, Ferris FL III. Report From the NEI/FDA Diabetic Retinopathy Clinical Trial Design and Endpoints Workshop. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5127-5142. doi: 10.1167/iovs.16-20356. PMID: 27699406; PMCID: PMC6016432.  FDA accepts improvement OR worsening (prevention of progression)1 of the disease AND DRSS is an established surrogate endpoint for DR 
 
 24  8%  16%  18%  32%  20%  6%  0%  0%  11%  36% 36%  34% 34%  28%  17%  11%  9%  0%  5%  10%  15%  20%  25%  30%  35%  ≥ 4 Steps Worsening  ≥ 3 Steps Worsening  ≥ 2 Steps Worsening  ≥ 1 Steps Worsening  No Change  ≥ 1 Step ≥ 2 Step ≥ 3 Step ≥ 4 Step Improvement Improvement Improvement Improvement  Percent of Subjects (%)  Placebo (n=50)  APX3330 (n=47)  DRSS Worsening  DRSS Improvement  Percent of Subjects with Binocular Improvement or Worsening in DRSS at Wk 24  APX3330 Demonstrated Statistical Efficacy on the Pre-Specified, Planned Phase 3 Registration Endpoint  Percent of Subjects With Binocular Improvement or Worsening in DRSS of ≥ 1, ≥ 2, ≥ 3, and ≥ 4 Steps From Baseline (mITT-LOCF)  40%  ZETA-1 Clinical Trial; p values shown if p<0.20  Table 14.2.2.7, March 2023  p<0.05  p=0.18  2% 
 
 25  Change in DRSS Score by Patient by Eyes  0% Patients in APX3330 Treatment Group had Binocular 3-Step Worsening  DRSS Bar Legend  Green: Both Eyes Improving  Blue: 1 Eye Improving and 1 Eye Unchanged Purple: 1 Eye Improving and 1 Eye Worsening Orange: no change OU  Gray: 1 Eye Worsening and 1 Eye Unchanged Red: Both Eyes Worsening  Patients (n=47) Patients (n=47)  -3  3  Presented on 8/1/23 at ASRS 
 
 26  Change in DRSS Score by Patient by Eyes  16% Patients in Placebo Treatment Group had Binocular 3-Step Worsening  Patients (n=50)  DRSS Bar Legend  Green: Both Eyes Improving  Blue: 1 Eye Improving and 1 Eye Unchanged Purple: 1 Eye Improving and 1 Eye Worsening Orange: no change OU  Gray: 1 Eye Worsening and 1 Eye Unchanged Red: Both Eyes Worsening  -3  3  Presented on 8/1/23 at ASRS 
 
 27  % of Subjects With Binocular ≥ 3-Step Worsening in DRSS and Progression to PDR  APX3330 Prevented Progression of Structural Retinal Abnormalities  16%  0%  0%  0%  5%  10%  15%  20%  Percent of Subjects (%)  Visit  Placebo  (N=49)  APX3330  (N=46)  Week 12  n=50 n=47  12%  p=0.07  Percent of Subjects With Worsening in DRSS of ≥3 Steps From Baseline by Visit Binocular Eyes (mITT-LOCF)  It is estimated ~25% of untreated patients may progress by ≥ 3 steps in binocular DRSS over 1 year1  ZETA-1 Clinical Trial  1 Sun JK, Evidence for DR Progression and Regression from Clinical Trials. Presented at NDI/FDA DR Clinical Trials Design and Endpoints Workshop, June 26, 2015.   24%   14%  0  5  10  15  20  25  30  Placebo  (n=49)  (n-48)  Subjects Developing PDR (%)  (n=48)  (n=50) APX 3330  Treatment Group  p=0.22  Percentage of Subjects Developing PDR (mITT Population) at week 24  APX3330 reduced the percentage of subjects who developed PDR over the course of 24 weeks  Week 24  n=50 n=47   19%   5%  0%  5%  10%  15%  20%  25%  % of Subjects  Placebo (n=43) APX3330 (n=40)  Treatment Group  p=0.07  Percentage of Subjects with ≥ 5 Letters of BCVA Lost at Week 24  (Safety Population)  BCVA data shows fewer APX3330 treated subjects losing visual acuity compared to placebo at week 24  p=0.04 
 
 28  APX3330 SAEs: Dyskinesia, TIA, Chest pain  Placebo SAEs: Vertigo, Asthenia, Multiple organ dysfunction, Bradycardia, CAD, Cholelithiasis, COVID-19 pneumonia, Cellulitis, Respiratory failure, Skin ulcer, Peripheral embolism  AEs → Withdrawal APX3330: Presyncope, Dyspnea; Placebo: DME (both eyes)  *Preferred Term within Organ Class  ZETA-1: Treatment Emergent Adverse Events  Oral APX3330 Showed a Favorable Safety and Tolerability Profile Consistent with Prior Trials  Placebo (n=52)  APX3330 (n=51)  Total AEs  120  91  #of Subjects with AEs  35 (67%)  29 (57%)  Treatment-related AEs  17 (14%)  14 (15%)  Serious AEs  11 (9%)  3 (3%)  Subjects Withdrawals Due to AEs  1 (2%)  2 (4%)  Deaths  1 (2%)  0 (0%)  AEs in >5% of Subjects*  Diabetic Retinal Edema  5 (10%)  2 (4%)  Diabetic Retinopathy  6 (12%)  1 (2%)  Vitreous detachment  3 (6%)  0 (0%)  Cataract  1 (2%)  3 (6%)  Pruritus  1 (2%)  6 (12%)  Rash  1 (2%)  3 (6%)  COVID-19  5 (10%)  1 (2%)  APX3330 Safety Profile:  Limited AEs, most mild in severity  Pruritis: Mild and resolved without APX3330 dose de-escalation or discontinuation  AEs similar to or less than placebo  Few serious treatment-related AEs, all unrelated to study medication  No ocular AEs other than expected DR progression  Lower incidence of clinical DR/DME worsening with APX3330  Patients continued routine medications to manage their diabetes comorbidities  | Eye disorders | 
 
 29  APX3330 - Phase 2 Summary and Next Steps  APX3330 demonstrated favorable safety and tolerability with compelling potential to slow progression of diabetic retinopathy  ZETA-1 statistically significant results on potential Phase 3 registration endpoint:  0% APX3330-treated patients had a binocular ≥ 3-step worsening of DRSS from baseline compared with 16% for placebo-treated patients (p=0.04)  ZETA-1 Summary  Further analysis of ZETA-1 Phase 2 data, including insights for Phase 3 trial design  Prepare for EOP2 FDA meeting in Q4 2023 to formally confirm Phase 3 design and registration endpoint  Advance APX3330 into Phase 3 program with long-term exposure (up to 2 years)  APX3330 Next Steps  To have a clinically meaningful impact on preventing progression to reduce likelihood of vision loss in diabetic retinopathy patients  Our Goal for Patients 
 
 DR is one of the largest markets in retina with 10M patients in US and over 100M worldwide  Majority of the NPDR patients are not candidates for approved biologics treatments and are left untreated  APX3330 first-in-class oral drug that inhibits Ref-1 which reduces VEGF and inflammatory cytokines to normal physiological levels  Prevention of worsening is a clinically meaningful potential registration endpoint that was met in ZETA-1 study  No subjects (0%) treated with APX3330 had a binocular ≥ 3-step DRSS worsening from baseline compared with 16% for placebo (p=0.04) after 24 weeks of treatment  APX3330 demonstrated favorable safety & tolerability in diabetic patients  An EOP2 meeting with FDA is confirmed in Q4 2023  APX3330 has the potential to be an early, non-invasive preventative treatment for the 8 million NPDR patients with the potential to treat other organs affected by diabetes (e.g., kidney disease, peripheral neuropathy)  Broad prescriber base including general ophthalmology, optometry and primary care due to favorable safety  30  APX3330 Key Takeaways 
 
 31  Nyxol 
 
 32  Global Partnership with Viatris for Nyxol  Viatris Has Selected Nyxol to be a Key Element of its Global Eye Care Division  Fully funded development and commercialization costs for all 3 Nyxol indications  Partner for Nyxol global commercialization  Allows Ocuphire to focus on APX3330 development  Strengthens cash position into 2025  $35 million upfront  Funding for potentially all R&D and commercialization for all 3 indications globally  $130 million in regulatory and sales milestones  First potential $10 million milestone payment on FDA approval in RM  Tiered double digit royalties through 2040 
 
 33  Reversal of Mydriasis (RM)  P  DLD  Dim Light or Night Vision Disturbances (DLD)  Presbyopia  Nyxol as a Single Drop  Nyxol with LDP Adjunctive Therapy  1  0.4%  2  RM  R  M  NYXOL®  EYE DROPS  THREE INDICATIONS  NEW PARTNERSHIP WITH VIATRIS 
 
 34  Summary of Nyxol Trial Results  Comprehensive Body of Clinical Data Supporting Efficacy and Safety Across 3 Indications  Indication & Status  Primary Endpoint  Efficacy Data  Key Secondary Endpoint(s)  Safety & Tolerability  RM  PDUFA 9/28/23  Return to baseline pupil diameter at 90 minutes after dilation  Met Phase 3 primary endpoint MIRA-3: 58% Nyxol vs. 6% placebo  MIRA-2: 49% Nyxol vs. 7% placebo (p<0.0001)  MIRA-4: 64% Nyxol vs. 25% placebo  Efficacy across all mydriatic agents, iris color, 1 or 2 drops, and all ages (3-80)  Presbyopia (Nyxol Alone)  Phase 3  ≥3 line gain in near vision with loss of no more than 1 line in distance vision  Met planned Phase 3 primary endpoint VEGA-1: 29% Nyxol vs.12% placebo at 12 hrs post-Nyxol dose  (p=0.02)  Durable near vision (18 hrs) Optimal pupil size Pupillary light reflex  No headaches  No blurry vision  ~5% mild redness  No change in IOP  No SAEs  Most AEs were mild  Presbyopia (Nyxol + LDP)  Phase 3  Met Phase 2 primary endpoint  Met planned Phase 3 primary endpoint VEGA-1: 61% combo post-LDP dose (30 min) + post-Nyxol dose (12 hrs)  vs. 14% placebo (p<0.0001)  Durable near vision gain Optimal pupil size Pupillary light reflex  DLD  2nd Phase 3  ≥3 lines (eye test) of improvement in mesopic low contrast best-corrected distance visual acuity (mLCVA)  Met Phase 3 primary endpoint LYNX-1: 13% Nyxol vs. 3% placebo at Day 8 (p<0.05) and 21% in Nyxol vs.3%  placebo at Day 15 (p<0.01)  Improvement visual acuity measures (distance and near) in dim light conditions 
 
 35  Corporate Highlights  Late-Stage Retinal Pipeline Represents Multi-Billion Dollar Opportunity in Unmet NPDR Patients  APX Pipeline Driven by a Paradigm Changing, Dual Target Ref-1 Platform for Retinal Diseases  Global License Agreement with Viatris to Fund Development and Commercialization of Nyxol for All Refractive Indications  Strong Financial Position to Fund Operations into 2025  APX3330 – Novel, Non-Invasive, Safe Oral Tablet to Treat Diabetic Retinopathy 
 
 Restore Vision & Clarity  www.ocuphire.com ir@ocuphire.com  Ocuphire Pharma  Appendix  36 
 
 37  Silva et al. ARVO 2021 Annual Meeting  *Published data on EYLEA. This study was performed independently from APX3330 study and is a cross-study comparison.  **Li 2014; *** Pasha 2018; ****Jiang 2011 (Vldlr -/- : Very Low-Density Lipoprotein receptor knock-out mice)  Preclinical Data: Oral APX3330 Blocks Neovascularization  Lesion Volume Decrease with Oral APX3330 in Murine Laser CNV Model Similar to EYLEA® Data  L-CNV Mouse Retina Model  Lesion Size and Corresponding Fluorescent Stains in L-CNV Models Treated with APX3330 at 25 mg/kg oral gavage  APX3330 APX3330 Gavage OCT  Vehicle 25 mg/kg 50 mg/kg Lesion Volume  -55%  Silva et al, 2021  L-CNV Mouse Retina Model  *EYLEA  Efficacy was also seen after single intravitreal injection of 20µM APX3330 in mouse L-CNV model**  Efficacy was also seen after dosing intraperitoneal injection of 50 mg/kg twice daily, 5 days on/2 days off, for 2 weeks in mouse L-CNV model***  Efficacy was also seen after single intravitreal injection of 20µM APX3330 in Vldlr -/- mice model****  -44% 
 
 38  505(b)(2) Regulatory Pathway Supported by Prior Phentolamine Approvals in non-ophthalmic Indications  Illustration for educational purposes  Nyxol’s Differentiated MOA as an Alpha-1 Blocker  No Engagement of Ciliary Muscle, No Headaches and Lower Risk of Retinal Detachment  Phentolamine is the Active Ingredient in Nyxol: a non-selective α Antagonist  Phentolamine blocks α1 receptors on the  Iris Dilator Muscle up to 24 hours  Decreases pupil size (moderately)  without affecting the iris sphincter or ciliary muscles  Allows for 3 indications:  RM, Presbyopia and DLD 
 
 39  Phase 2  Phase 1  Ocuphire  Nyxol + 0.4% pilo  Visus Brimochol® (carbachol + brim)  Other Cholinergic Agonists*  Cholinergic Agonist* (pilocarpine)  Lenz Aceclidine; Aceclidine + brim  Eyenovia  MicroLine (2% pilo)  Alpha Antagonist & low dose pilocarpine*  Alpha Antagonist  NDA  Allergan  VUITYTM;  (1.25% pilo)  Orasis  CSF-1 (Low dose pilo)  Phase 3  Nyxol’s potential differentiation:  New MOA class (iris dilator muscle inhibitor)  Favorable safety and tolerability (e.g.: no headaches, no accommodative spasm, no risk of retinal detachment)  24-hour durability  Broad range of patients including high myopes  Improvement in night vision disturbances  Nyxol+LDP may offer added efficacy and tunability  Ocuphire  Nyxol  (0.75% phentolamine)  Pupil modulation MOA  Combination drugs  Lens softening MOA  X  Novartis  EV-006  Lens Softening  * acts on sphincter and ciliary muscles in dose- dependent manner  Corporate Websites as of July 31, 2023,  Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020  A New, Differentiated MOA and Combination Therapy Offers Tunability 
 
 40  Management Team with Decades of Drug Development Experience  Drey Coleman  VP, Clinical Operations  Amy Rabourn, CPA  SVP, Finance  Charlie Hoffmann, MBA  SVP, Corporate Development  Mitch Brigell, PhD  Head, Clinical Development  and Strategy  Daniela Oniciu, PhD Global Head, R&D, Chemistry and Product Development  Ronil Patel, MTech, MS  SVP, Operations and BD  Chris Ernst Global Head, QA and Manufacturing  Barbara Withers, PhD  VP, Clinical and Regulatory Strategy  Bindu Manne Head, Market Development and Commercialization  Laura Gambino  Director, Project Management  Richard Rodgers, MBA  Interim CEO 
 
 41  Ocuphire's World-Class Medical Advisory Board  Chief Medical Advisor, Ocuphire Refractive Specialist  Jay Pepose, MD, PhD UCLA School of Medicine  Refractive Specialist  Y. Ralph Chu, MD Northwestern University  Refractive Specialist Zaina Al-Mohtaseb, MD  Baylor College of Medicine  Refractive Specialist James Katz, MD University of Illinois  Refractive Specialist Marguerite McDonald, MD Columbia University  Refractive Specialist  Mitch Jackson, MD University of Chicago  Refractive/ Glaucoma Specialist  Thomas Samuelson, MD  University of Minnesota  Refractive/Glaucoma Specialist  Inder Paul Singh, MD The Chicago Medical School  Eliot Lazar, MD Georgetown University  elCON Medical  Retinal Specialist Peter Kaiser, MD Harvard Medical School  Retinal Specialist  David Lally, MD Vanderbilt University  Retinal Specialist  Michael Allingham, MD, PhD University of North Carolina  Retinal Specialist David Boyer, MD  Chicago Medical School  Retinal Specialist David Brown, MD Baylor University  Retinal Specialist Jeffrey Heier, MD Boston University  Retinal Specialist  Anat Lowenstein, MD, PhD The Hebrew University  Retinal Specialist  Caroline Baumal, MD University of Toronto Medical School  Optometry  Douglas Devries, OD University of Nevada  Optometry  Paul Karpecki, OD Indiana University  Optometry  Justin Schweitzer, OD Pacific University College of Optometry  Optometry  Selina McGee, OD Northeastern State University  Optometry  Leslie O’Dell, OD Salus University  Co-Founder Apexian/APX3330  Mark Kelley, PhD Indiana University 
 
 42  Ocuphire Board of Directors  Sean Ainsworth, MBA  Lead Independent Director,  Board Director  Jay Pepose, MD, PhD  Board Director  Susan Benton, MBA  Board Director  Cam Gallagher, MBA  Chair, Board Director  James Manuso, PhD/MBA  Board Director  Richard Rodgers, MBA  Interim President & CEO  Board Director