Form: 8-K

Current report filing

January 6, 2021


Exhibit 99.1

 Ocuphire Corporate Presentation  January 2021   
 

 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 Ocuphire Pharma, Inc.’s (“Ocuphire” or the “Company”) product candidates and potential.  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) potential adverse reactions or changes to business relationships resulting from the announcement or completion of the merger; (ii) the success and timing of regulatory submissions and pre-clinical and clinical trials; (iii) regulatory requirements or developments; (iv) changes to clinical trial designs and regulatory pathways; (v) changes in capital resource requirements; (vi) risks related to the inability of the Company to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vii) legislative, regulatory, political and economic developments, and (viii) the effects of COVID-19 on clinical programs and business operations. 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  may not be reproduced or provided to any other person (other than your advisor) without our prior written consent.  By accepting delivery of this presentation, you agree to the foregoing and agree to return this presentation and any documents related thereto and any copies thereof to us or to destroy the same if you do not make an investment in any securities. The information contain within this presentation shall not, except as hereinafter provided, without the prior written consent of the Company, be disclosed by you or your representatives in any manner whatsoever, in whole or in part, and shall not be used by you or your representatives other than for the purpose of evaluating the transaction described herein.  By accepting delivery of this presentation you further acknowledge and agree aware of the restrictions imposed by the United States securities laws on the purchase or sale of securities by any person who has received material, nonpublic information from the issuer of the securities or any affiliate thereof and on the communication of such information to any other person when it is reasonably foreseeable that such other person is likely to purchase or sell such securities in reliance on such information for so long as the information remains material and non-public. 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.   November 6, 2020 
 

   Late Clinical Stage Company Targeting Large, Unmet Ophthalmic Markets   Significant Clinical Data and Regulatory Precedents  Significant IP Portfolio and Small Molecule CMC Advantages  Multiple Near-Term Data Catalysts with Capital Efficient Plan  Nyxol eye drops target multiple chronic and acute front of the eye indications addressing large markets: Dim Light / Night Vision Disturbances (NVD), Reversal of Mydriasis (RM), & Presbyopia (P)APX3330 tablets target chronic back of the eye indications: Diabetic Retinopathy (DR) and Diabetic Macular Edema (DME), a leading cause of blindness in diabetic patients  Nyxol and APX3330 achieved promising clinical data over multiple Phase 1 and 2 trialsNyxol with > 150 patients treated across 7 trialsAPX3330 with > 340 patients treated across 11 trialsFDA End of Phase 2 meeting guidance for Nyxol (all indications) in May 2020  US and global issued patents thru 2034 obtained for both assetsStable, small-molecule drugsNyxol = single-use, preservative-free eye dropAPX3330 = oral pill  4 late-stage trial readouts (2 Phase 3, 2 Phase 2) expected in 1Q through 4Q 2021$20+M financing provides sufficient cash to run capital-efficient ophthalmic-focused operations in 2021Analyst research coverage initiated by Cantor Fitzgerald and Encode IdeasNyxol NDA filing in one or more indications targeted for early 2023    Ocuphire Opportunity  A Late-Stage Clinical Ophthalmic Biotech (Nasdaq Symbol: OCUP)   Nyxol®  APX3330 
 

 Ocuphire Management Team    Decades of Biotech and Drug Development Experience        Amy Rabourn, CPAVP Finance  Daniela Oniciu​, PhDHead CMC and Global Clinical Supply  Kostas Charizanis, PhD, MBASenior Director Market Strategy and R&D    Mitch Brigell, PhDHead Clinical Development and Strategy    Laura GambinoProject Management ​    Drey ColemanDirector Clinical Operations and Vendor Management    Charlie Hoffman, MBAVP Corporate Development and Operations    Mina Sooch, MBAPresident & CEO and Founder     
 

 Large Unmet Opportunities for the Aging Eye    Source: GlobalData Market Research Report, 2020  Developing Drugs to Treat Front & Back of the Eye Diseases       Back  Front  PresbyopiaU.S. Prevalence: ~120M  Night Vision DisturbancesU.S. Prevalence: ~16M adults  Reversal of Mydriasis~100M pupil dilations per year in U.S.  Nyxol®  APX3330  $4-10B US Markets  $4-10B US Markets  Diabetic Macular EdemaU.S. Prevalence: ~750K  Diabetic RetinopathyU.S. Prevalence:~ 7M 
 

     Product Candidate  Indication  Development Stage        Anticipated Milestones        Pre-clinical  Phase 1  Phase 2  Phase 3    Ocuphire-Focused Development  0.75% Nyxol®Eye Drop  Dim Light or Night Vision Disturbances (NVD)          Initiated Phase 3 LYNX-1 trial 4Q2020;Data expected in 3Q21 (n=160)    0.75% Nyxol®Eye Drop  Reversal of Mydriasis (RM)          Initiated Phase 3 MIRA-2 trial 4Q2020; Data expected in 1Q21 (n=168)    0.75% Nyxol® + Low-Dose 0.4% Pilocarpine Eye Drops  Presbyopia (P)          Initiate Phase 2 VEGA-1 trial 1Q2021;Data expected in 2Q21 (n=152)    APX3330 Oral Pill  Diabetic Retinopathy (DR)/ Macular Edema (DME)          Initiate Phase 2 ZETA-1 trial 1Q2021;Data expected in 4Q21 (n=100)  Partnering-Focused Development  APX2009 Intravitreal  DME, Wet Age-Related Macular Degeneration (wAMD)          Next steps: IND enabling studies  (with partner funding)    Combo (0.75% Nyxol® +  Latanoprost) Eye Drops  Glaucoma          (16 to 24 mmHg)          Next steps: 2nd line add-on Phase 2 trial (with partner funding)    Ocuphire Pipeline & Upcoming Milestones    Multiple Phase 3 & Phase 2 Clinical Data Catalysts Expected Throughout 2021  Enrollment Complete          Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution) 
 

 11Phase 1 & Phase 2 Trials  >340Subjects Dosed  Exposure in Humans 365 Days   Patents to2034+    Extensive Development on Both Drug Candidates     Well-Controlled Phase 1 & Phase 2 Clinical Programs Set Stage for NDA Path  NCE Development Pathway  Studied in inflammation/hepatitis & cancer patients   7Phase 1 & Phase 2 Trials  > 150Subjects Dosed  Exposure in Humans28Days   Patents to2034+    505(b)(2) Development Pathway  Studied in ocular refractory diseases (NVD) & elderly glaucoma patients  Nyxol  APX3330 
 

   Nyxol®  Phentolamine Mesylate  NVD  Night Vision Disturbances  P  Presbyopia  RM  Reversal of Mydriasis 
 

 Nyxol History & MOA  Nyxol’s active ingredient, phentolamine mesylate (PM), is currently approved for 2 indicationsPheochromocytoma (60+ years ago, Regitine®) – intravenous injectionReversal of oral anesthesia (10+ years ago, OraVerse®) – intramuscular injectionPM has been reformulated as a topical eye drop (Nyxol)Nyxol is a first-in-class non-selective α1 and α2 blocker product candidateMOA of relaxing the iris dilator muscle (α1)Redness is an on-target α1 effect on sclera vessels (transient, mild)     Rationale for Differentiated Product Profile & 505(b)(2) Path    Phentolamine Mesylate  Reduces Pupil Size   Dilates Blood Vessels (Vasodilation)  α1: Smooth Muscle Blockade  α1: Iris Dilator Blockade 
 

 Improving Vision↓ Pupil Size (moderate miotic)↑ Contrast Sensitivity (night)↑ Near Visual Acuity (light/dark)↑ Distance Visual Acuity  No Systemic EffectsNo Changes in Blood PressureNo Changes in Heart RateTolerated Topical EffectsMild / Transient / Reversible Eye RednessIOP Unchanged or Decreased↓ Intraocular Pressure (IOP) at Normal Baseline  Nyxol Product Candidate Profile  First-in-Class Alpha 1/2 Blocker Eye Drop for Refractory Indications  Safety Data  Efficacy Data  Nyxol: Phentolamine 0.75% Ophthalmic SolutionPreservative Free, EDTA Free, and Stable  Chronic daily dosing of Nyxol at bedtime demonstrated no significant daytime redness and durability of effects for more than 24 hours   
 

 Moderate-to-Severe NVDs  US Patients  Night Myopia  10.8M  Cortical Cataracts  4.1M  Post-LASIK  500k  Post-IOL Implant  300k  Total  ~16M  Night Vision Disturbances (NVD) – Chronic Opportunity  Peripheral imperfections scatter light when pupils enlarge in dim light, causing halos, starbursts, and glare that impair visionThe imperfections may be caused by LASIK surgery, IOL implants, certain types of cataracts (cortical), and natural reasons (especially with age) Symptoms cannot be properly corrected by any type of lens (reading glasses, contact lenses) or surgical procedures  Source: GlobalData Market Research Report, 2020  The Problem  Imperfections in the Eye Affect Night Vision in Millions     No Currently Approved Therapies  NVD  I’m no longer comfortable driving at night, especially with my son in the car. I have a hard time playing beach volleyball in the evenings due to the bright lights at the courts.  Post-LASIK, aged 42     
 

 Night Vision Disturbances (NVD) – Chronic Opportunity  Moderate Decrease in Pupil Size for scattered light gets blocked by the iris Clinical Effect to potentially improve low contrast night vision as seen in trialsTolerable with a minimal side effect profile Convenient and Durable with chronic once-daily evening dose  Nyxol’s Potential Differentiated Solution   Peripheral Optical Imperfections Allowing Pupil Modulation as a Solution    After  Before  NVD  Once there is a drug and a category, that’s when they start looking for the disease.  Physician KOL      Seeking Treatment Findings    Patients willing to try a new eye drop treatment  67%  Patients avoiding driving at night  25% 
 

   NVD LYNX-1 Phase 3 Registration Design  Randomized, Double-Masked, Placebo-Controlled Two-Week Trial  LYNX-1  Primary: % of subjects with ≥ 3 lines of improvement in mesopic low contrast best-corrected distance visual acuity (Day 8)Secondary (Days 8 & 15):Pupil diameterVisual acuity measures (distance and near)Safety and tolerability (redness)  Endpoints  Eligibility Screening  Randomization  1:1  daily evening dose(14 days)  daily evening dose (14 days)  0.75% Nyxol   Placebo  15 US sites~160 patients with NVD  NVD  Phase 3 Initiated in Late 4Q20  Top Line Expected 3Q21   
 

     ORION-1 Phase 2 Trial  NYX-SNV Phase 2 Trial  Nyxol Demonstrated Clinical Effect in NVD  Key Endpoints Observed in Multiple Phase 2 Trials  Improved Low Contrast Distance Visual Acuity*  Source: NYXG-201  Durable > 24 hour Pupil Modulation Effect  % of Eyes with Mesopic Low Contrast Visual Acuity Improvement  Pupil Diameter Change from Baseline in Mesopic Conditions (Study Eye)  Source NYX-SNV  % of Subject Eyes  p=0.029  p=0.04  p=0.16    Pupil Diameter Change from BaselineANCOVA (mm)  Baseline Pupil Diameter: Placebo 4.6mm, Nyxol 4.7mm  NVD  *NYX-SNV trial was small and not designed for a statistical 3-line improvement in low-contrast visual acuity; the 20% effect was used for powering and sizing of Phase 3 trial 
 

 Reversal of Mydriasis (RM) – Acute Treatment   At every annual eye exam and many specialty visits, pupils are pharmacologically dilated, impairing vision for 6-24 hoursDilated eyes:heightened sensitivity to light inability to focus reading, working, and driving are difficult halos and glare  The Problem  Annual Exams and Specialty Visits Involve Dilation to Monitor Eye Health  ~100M eye exams / year in US  No Currently Approved Therapies  RM  Source: GlobalData Market Research Report, 2020  I have to stay indoors. They say it only lasts a few hours, but it lasts all day, and it is very annoying.  RM Patient, Aged 51     
 

 After  Before  Reversal of Mydriasis (RM) – Acute Treatment   Regulatory Precedent with RevEyes (an alpha 1 blocker), approved by the FDA in 1990 but shortly thereafter discontinued (not for safety or efficacy reasons)Clinical Effect to potentially reduce pupil size and reverse mydriasis by counteracting the drugs (alpha agonists and cholinergic blockers) used to dilate the pupilConvenient eye drop given at the office that may allow vision to return to normal soonerTolerable with a minimal side effect profile (unlike cholinergic agonists such as pilocarpine)  Nyxol’s Potential Differentiated Solution  Single Use Indication Leveraging a Precedent Approval Pathway  RM  Seeking Treatment Findings    Patients likely to request reversal of dilation  45%  Eye care providers likely to use reversal drops  40%  Source: GlobalData Market Research Report, 2020 
 

 RM MIRA-2 Phase 3 Registration Design  Randomized, Double-Masked, Placebo-Controlled, Parallel, One-Day Trial  MydriasisTime -1 Hour  MIRA-2  1:1  Mydriatic Agent A, B, or C  0.75% Nyxol   Placebo  12 US sites~168 healthy subjects  Nyxol drop(s)(1 day)  Mydriatic Agent A, B, or C  Placebo drop(s)(1 day)  Treatment Time 0 (Max Dilation)  RM  Primary: % of subjects returning to baseline (within 0.2 mm) pupil diameter at 90 minSecondary:% of subjects returning to baseline at 30min, 1h, 2h, 3h, 4h, 6h, 24hMean change in pupil diameter from mydriatic max at all timepointsAccommodation (tropicamide)Safety and tolerability (redness)  Endpoints  Started and Completed Enrollment in 4Q20 – 185 Subjects  Top Line Expected 1Q21  Eligibility Screening  Randomization  Mydriatic Agents: phenylephrine (alpha agonist), tropicamide (cholinergic blocker), Paremyd® (combination)    1:1 
 

   Nyxol Demonstrated Clinical Effect in RM    Key Endpoints Observed from MIRA-1 Phase 2b Trial  MIRA-1 Phase 2 Trial  Nyxol Reduced More Subjects to Pupil Diameter (PD) Baseline  Source: MIRA-1  Nyxol Reduced PD Faster Across Phenylephrine & Tropicamide Mydriatic Agents   Source: MIRA-1  RM  Percent of Subjects Returning to ≤ 0.2 mm of Baseline after TreatmentWith either Phenylephrine or Tropicamide  Reduction in Pupil Diameter after Patients received eitherPhenylephrine 2.5% or Tropicamide 1.0% in Study Eye  Percent of Subjects (%)  p=0.1094  p=0.0262  p=0.0001    Pupil Diameter (mm)  *p<0.05; **p<0.01; ***p<0.001; ****p<0.0001    MIRA-2 protocol enhancements:1  2 drops of Nyxol in study eye AND dark irides  dark/light irides 
 

 Presbyopia – Chronic Opportunity  Lens loses ability to change shape when viewing objects up close as we ageDependence on reading glasses for intermittent and prolonged useGrowing need for therapies that improve, rather than hinder, quality of life  Source: GlobalData Market Research Report, 2020  The Problem  Aging Population Drives Demand for Alternatives to Reading Glasses  P  120 M Patients  No Currently Approved Drug Therapies  Effectively everyone over 40 will have the problems with reading.  Physician KOL      Seeking Treatment Findings    Patients requesting alternative to reading glasses  40%  Patients would consider an eye drop alternative  69% 
 

 Presbyopia – Chronic Opportunity  “Pin-hole” effect of Nyxol and low dose pilocarpine may improve near vision by increasing depth of focus as validated by other devices/therapiesMore durable combination of two miotics affecting different muscles (iris dilator and sphincter) involved in pupil size modulationTolerable use with minimal side effects expected with chronic evening use of Nyxol  Retinaeyedoctor.com, GlobalData Market Research Report, 2020  Nyxol’s Potential Differentiated Solution  Pupil Modulation Eye Drops May Replace Reading Glasses    Large Pupil  Pin-hole Pupil  Near  Far  In focus  In focus  P  This would just become part of my daily routine for my eyes to be able to see things up close. How convenient is that?  Presbyopic Patient, age 49     
 

 Presbyopia VEGA-1 Phase 2 Proposed Design  Planned Randomized, Double-Masked, Placebo-Controlled One-Week Trial  Visit 1    VEGA-1  Eligibility Screening  Randomization  4 arms  0.75% Nyxol   Placebo  20 US sites~152 presbyopic patients  Visit 2 (3 – 5 Days Later)  Screening  P  Primary: % of subjects with ≥ 3 lines of improvement in distance-corrected near visual acuity comparing Nyxol + LDP vs placebo alone at 1 hourSecondary:% of subjects with ≥ 2 and ≥ 3 lines gained at time points from 30 min to 6 hours in photopic and mesopic lighting comparing Nyxol + LDP vs placebo, Nyxol alone, and LDP aloneNo loss of distance vision Pupil diameter at time pointsSafety and tolerability (redness)  Endpoints  Phase 2 Start Targeted for 1Q21  Top Line Expected 2Q21  LDP= low-dose pilocarpine (0.4%)  Treatment Arms  Nyxol + LDP  LDP Drop  Nyxol  Baseline  Nyxol Alone  No Treatment  Nyxol  Baseline  LDP Alone  LDP Drop  Placebo   Baseline  Placebo Alone  No Treatment  Placebo   Baseline 
 

   Nyxol Demonstrated Clinical Effect in Presbyopia    Key Endpoints Observed from Multiple Phase 2 Trials  Average pupil size in photopic conditions is 3.5 to 4+ mm    Source: ORION-1  0.4%            1.5 to 2+ mm PD reductionAchieve the pin-hole (1.6 to 2 mm) effect   Nyxol Alone  LDP Alone  Near VA Line Improvement at Day 15(Full Analysis Set, Study Eye, Photopic)  ~0.7 to 1+ mm  P  ORION-1 Phase 2 Trial  Improvements in DCNVA with Nyxol AloneWith No Change in Distance Vision  Pinhole PD Size Illustrated with Addition of LDP to Nyxol  Percent of Subjects with VA Line Improvements  *p=0.026  ~0.7 to 1+ mm     
 

         Phase 3  Phase 2  Phase 1  Presbyopia Eye Drops Competitive Landscape  An ideal formulation for presbyopia treatment would meet the following criteria: Comfort and tolerabilityFast onsetLong durationEfficient pupil size modulationStrong safety profileMaintain good distance visual acuity  Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020  Validation of Pupil Modulating Drops Achieving Pin-Hole Effect & Efficacy, Many with Pilocarpine  Pupil modulation MOA    Combination drugs      Soften lens MOA          Phase 3  Phase 2  Phase 1  Allergan(AGN-190584;1.25% pilo)      Orasis(CSF-1; Low dose pilo)    Ocuphire(0.75% Nyxol + 0.4% pilo)    Visus(Brimochol®; brimonidine + carbachol)  Other Cholinergic Agonists*  CholinergicAgonist* (pilocarpine)  Presbyopia Therapies(PRX-100; aceclidine)      Eyenovia(MicroLine;1 or 2% pilo)    Novartis(EV-06)  Alpha Antagonist& pilocarpine*  P    NDA  *act on sphincter and ciliary muscles in dose-dependent manner 
 

   APX3330  APX3330  DR  Diabetic Retinopathy  DME  Diabetic Macular Edema  wAMD  Wet Age-Related Macular Degeneration 
 

 APX3330 is a Ref-1 Inhibitor  Ref-1 Involved in Multiple 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-αChemokines  Neovascularization  Lucentis®EYLEA®  Anti-VEGF    Steroids    APX3330  Logsdon et al (2018), Li et al (2014).  APX3330 is a small molecule oral drug candidate and a first-in-class inhibitor of Ref-1Ref-1 (reduction-oxidation effector factor-1) is a novel target discovered and characterized by Dr. Mark R. Kelley at Indiana University School of MedicineAPX3330 previously developed by Eisai for multiple hepatic inflammatory indications and later by Apexian for advanced solid tumorsSimilar oncology origin as approved anti-VEGFsMOA uniquely decreases both abnormal angiogenesis and inflammation by blocking pathways downstream of Ref-1 
 

 APX3330 Product Candidate Profile  First-in-Class Ref-1 Inhibitor Phase 2 Ready for Retina Diabetic Indications  Improving Eye Health in Diabetics ↓ Inflammation ↓ Hypoxia Signaling ↓ Abnormal AngiogenesisEnhance Compliance & ExposureOral pill may reduce the burden of frequent anti-VEGF injections  Few Systemic Adverse EffectsMild Gastrointestinal (diarrhea)Mild Skin Rash (Reversible)Lack of Significant Acute Neurologic, Cardiovascular, Liver, or Pulmonary toxicityNo Topical EffectsNo observed ocular AEs  Safety Data  Expected Efficacy Data  APX3330: 600mg Oral Dose (120mg or 300mg tablets)  Twice a day dosing of APX3330 being developed to providesteady state effectiveness with a tolerable chronic safety profile   
 

 Diabetic Eye Opportunity    DR  ~7.7M Patients  DME  ~750K Patients  Diabetic Retinopathy & Macular Edema  Diabetic retinopathy (DR) and diabetic macular edema (DME) are a leading cause of vision loss worldwide, especially in working age adults in developed countriesDiabetes damages small blood vessels within the eye causing leakage, oxygen starvation, and abnormal vessel growth, which can obstruct visionDR patients are not commonly treated with approved injectable anti-VEGF drugs given earlier stage of retinal disease and many are asymptomaticDR progresses in steps and may result in vision loss if left untreatedCurrent treatment for DME: 25% non-responders and 50% partial responders to anti-VEGF drugs  Sources: Global Market Insights Report 2019-2025, Market Watch 2019 Report, Gene.com Retinal Diseases Fact Sheet  The Problem  Non-Injectable Alternative Therapies are Needed For Earlier Stages of Disease  Injectable Anti-VEGF Approved TherapiesNot Commonly Used for NPDR  “Cotton Wool” Spots  Aneurysm  Hemorrhages  Diabetic Eye  Abnormal Blood Vessels  DR  DME 
 

 Diabetic Retinopathy & Macular Edema  Potential First Oral Therapy to be used as an earlier intervention for the diabetic eye before vision symptoms appear or as add-on therapy to current anti-VEGF treatmentProven Novel Mechanism that may decrease both inflammation and VEGF activityConvenient option for patients to potentially alleviate the burden of injections and increase complianceTolerable as seen in 11 completed Phase 1 and Phase 2 clinical trials  EYLEA Product Pamphlet  APX3330’s Potential Differentiated Solution  APX3330 to Treat Patients Before Vision Loss Occurs   DR  DME  DR  DME 
 

 DR/DME ZETA-1 Phase 2 Proposed Design  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)  Planned Randomized, Double-Masked, Placebo-Controlled 24-Week Trial    ZETA-1  Eligibility Screening  Randomization  1:1  Twice daily oral dose (24 weeks)  Twice daily oral dose (24 weeks)  APX3330 600mg  Placebo  15 US sites~100 patients with moderate-to-severe NPDR and mild PDR  DR  DME  Primary: % of subjects with a ≥ 2 step improvement on the DRSS (Diabetic Retinopathy Severity Scale) score at week 24Secondary:Central subfield thickness (CST)BCDVA (ETDRS)Safety and tolerabilityExploratory:Labs / PK  Endpoints  Phase 2 Start Targeted for 1Q21  Top Line Expected 4Q21 
 

 APX3330 Generally Well Tolerated with Clinical Signals    Observations from Pre-Clinical Studies and 11 Clinical Trials of APX3330  Source: Unpublished Data Dec 2019  Lesion Size and Corresponding Fluorescent Stains in L-CNV Models Treated with APX3330 at 25 mg/kg  Human Pharmacokinetics of APX3330 at 120 mg/day   Source: Unpublished Data Dec 2019  -55%  DR  DME      Phase 1 Clinical Trials  L-CNV Mouse Retina Model   APX3330 Reduces Neovascularization Similar to Eylea in Preclinical Models  Human Drug Exposure Multiple Times Higher than Mouse Efficacious Levels 
 

 Boards and Milestones   
 

   Richard Lindstrom, MDUniversity of Minnesota  Ed Holland, MDLoyola University Chicago  Jay Pepose, MDUCLA  Jack Holladay, MDUniversity of Texas  Thomas Samuelson, MDUniversity of Minnesota   Paul Karpecki, ODIndiana University  Eliot Lazar, MDGeorgetown University  Gary Novak, PhDUC Davis  Marguerite McDonald, MDColumbia University  David Boyer, MDChicago Medical School   Gerald Horn, MDUniversity of IllinoisCo-Founder Ocularis/Nyxol  Mark Kelley, PhDIndiana UniversityCo-Founder Apexian/APX3330  Prestigious Ocular Medical Advisory Board  Fortunate for the Insights of Leading KOLs & Drug Candidate Co-Founders  elCON Medical  Michael Allingham, MD, PhDUniversity of North Carolina  Richard Messmann, MDWayne State UniversityCMO Apexian/APX3330  Peter Kaiser, MDHarvard Medical School    Jeffrey Heier, MDBoston University  
 

 Ocuphire Board of Directors   Seasoned Directors with Decades of Biotech Drug Development and M&A/Financings          Sean Ainsworth, MBALead Independent Director, Board Director ​  James Manuso, PhD/MBABoard Director​  Alan R. Meyer, MBABoard DirectorMFR/IP Advisor​    Richard Rodgers, MBABoard Director     Susan Benton, MBABoard Director​    Cam Gallagher, MBAChair, Board Director    Mina Sooch, MBAVice-Chair, Board Director President & CEO 
 

   2020 to 2022 Cadence of Milestones  Multiple Data Catalysts for Value-Building  Nyxol NDA filing for RM & NVD in early 2023  Ongoing partnering discussions with leading ophthalmic companies (inc. European and Asian players)  NVD Podium Presentation at AAO 2018 Initiate/Report Phase 2b Data for ORION-1Initiate/Report Phase 2b Data for MIRA-1Expand Patent Estate  Completion of APX3330 LicenseARVO 2020 Presentation for MIRA-1ARVO 2020 Presentation for ORION-1FDA EOP2 Meeting May 2020  Announced Ocuphire Reverse Merger and PIPE Financing (Co-Led by Cantor and Canaccord)Completion of Transaction (Nasdaq: OCUP)Initiate Phase 3 RM TrialInitiate Phase 3 NVD TrialComplete Nyxol Market ResearchJournal Publications  Enrollment of Phase 3 RM trialInitiate Phase 2 Presbyopia TrialInitiate Phase 2 DR/DME TrialReport Phase 3 Data for RMEnrollment of Phase 2 Presbyopia trialReport Phase 2 Data for PresbyopiaNew Patent Claims  Enrollment of Phase 3 NVD trialReport Phase 3 Data for NVDEnrollment of Phase 2 DR/DME trialReport Phase 2 Data for DR/DMEReport 6-month Rabbit Tox StudyInitiate 2nd Phase 3 Trials for RM & NVD Initiate Acute and Chronic Phase 3 Safety Trial  Initiate Phase 3 Presbyopia TrialsReport 2nd Phase 3 Data for RM & NVDReport Phase 3 Safety DataReport Phase 3 Data for PresbyopiaInitiate Phase 3 DR/DME Trial(s)Industry/Journal PublicationsRegistration Batches for Nyxol Blow-Fill-Seal Eye Drops  2018/2019  1H 2020  2H 2020  1H 2021  2H 2021  2022   
 

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 NVD Endpoint: 5% Low Contrast Visual Acuity (LCVA) Chart  Precision Vision  FDA Accepted Endpoint for Contrast Sensitivity Assessment      Before Treatment*  3 Lines Improvement Illustration   Primary Endpoint of Nyxol LYNX-1 Trial Percent of subjects with ≥ 3 lines of improvement in mesopic low contrast best-corrected distance visual acuity (7 days)  * Inclusion Criteria includes subjects with baseline mesopic LCVA of 20/100 or worse   
 

       DR/DME Endpoint: Diabetic Retinopathy Severity Scale (DRSS)  EYLEA Product Pamphlet ®  FDA Accepted Endpoint for DR (EYLEA® in PANORAMA Pivotal Trial)  Patients included in the ZETA-1 Trial  Primary Endpoint of APX3330 ZETA-1 Trial Percent of patients with a ≥ 2 step improvement on the DRSS score at week 24  A 13-point Scale Outlining the Various Stages of Diabetic Retinopathy  DRSS Score  1 (10)  2 (20)  3 (35)  4 (43)  5, 6 (47, 53)   7 – 13 (60, 61, 65, 71, 75, 85,90)  Description  DR Absent  Micro-aneurysm only  Mild NPDR  Moderate NPDR  Moderately Severe NPDR  PDR – Mild, Moderate, and Severe  Retinal Image                Healthy blood vessels with no bulges  Small bulges in blood vessel walls as well as other signs in the retina  More changes in the blood vessels in the retina and small spots of blood can become more visible  More blood vessels in larger areas of the retina show changes  Many of the blood vessels in the retina show visible changes  Increased growth of new, damaged blood vessels