Form: 8-K

Current report filing

August 12, 2021



 Ocuphire Corporate Presentation  August 12, 2021  Mina Sooch CEO  Exhibit 99.2 
 

 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 future milestones, 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) timing or ability for the company to achieve its targeted milestones; (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, 2, and 3 trialsNyxol with > 330 patients treated across 9 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 for both assets; new 2039 Nyxol patent issued for presbyopia Stable, small-molecule drugsNyxol = single-use, preservative-free eye dropAPX3330 = oral pill  Initiated 4 late-stage trials (2 Phase 3, 2 Phase 2) with readouts expected in 2021-2022Reported positive P3 data in RM in 1Q21 with Nyxol NDA submission targeted late 2022Reported positive P2 data in Presbyopia in 2Q21 with plans to advance to P3 in 2022Recent $15M offering combined with cash on hand sufficient to run operations into late 2022Analyst coverage by Cantor, Canaccord, Jones Trading, Alliance Global, and Encode Ideas    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  Ronil Patel, MSSenior Director BD and Market Strategy    Mitch Brigell, PhDHead Clinical Development and Strategy    Chris ErnstQuality Assurance Lead    Drey ColemanHead Clinical Operations    Charlie Hoffmann, MBAVP Corporate Development and Operations    Mina Sooch, MBAPresident & CEO and Founder     
 

 Large Unmet Opportunities for the Aging Eye  Source: GlobalData Market Research Report, 2020; Company Estimates for Market Size  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  $10+ to $20+B US Markets  $4 to $10B US Markets  Diabetic Macular EdemaU.S. Prevalence: ~750K  Diabetic RetinopathyU.S. Prevalence:~ 7M  $325M- $1B  US Market Opportunity  $9B - $18B  $2B - $4B  $3B - $7B  US Market Opportunity  $1B - $3B           
 

   Product Candidate  Indication  Development Stage        Anticipated Milestones        Pre-clinical  Phase 1  Phase 2  Phase 3    Ocuphire-Focused Development  0.75% Nyxol®Eye Drop  Reversal of Mydriasis (RM)           Initiated Phase 3 MIRA-2 trial 4Q20; Topline data reported in 1Q21 (n=185)Initiate Phase 3 MIRA-3 trial 2H21; Data expected in early 2022 (n=330) Initiate Pediatric trial 2H21;Data expected in early 2022 (n=20)     0.75% Nyxol® + Low-Dose 0.4% Pilocarpine Eye Drops  Presbyopia (P)          Initiated Phase 2 VEGA-1 trial 1Q21;Topline data reported in 2Q21 (n=150)Initiate Phase 3 program in 1H22    0.75% Nyxol®Eye Drop  Dim Light or Night Vision Disturbances (NVD)          Initiated Phase 3 LYNX-1 trial 4Q20;Data expected in early 2022 (n=160)    APX3330 Oral Pill  Diabetic Retinopathy (DR)/ Macular Edema (DME)          Initiated Phase 2 ZETA-1 trial Apr21;Data expected in 2022 (n=100)  Partnering-Focused Development  APX2009 Intravitreal  DME, Wet Age-Related Macular Degeneration (wAMD)          Next steps: IND enabling studies  (with partner funding)    Ocuphire Pipeline & Upcoming Milestones    Multiple Phase 3 & Phase 2 Clinical Data Readouts Anticipated over the Next Year  Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution)   Positive Data Readout   Recruiting  Positive Data Readout   Recruiting       
 

 11Phase 1 & Phase 2 Trials  >340Subjects Dosed  Exposure in Humans 365 Days   Patents to2034+    Extensive Development on Both Drug Candidates     Well-Controlled Phase 1, 2, and 3 Clinical Programs with MIRA-2 Data Leading the NDA Path  NCE Development Pathway  Studied in inflammation/hepatitis & cancer patients   9Phase 1, Phase 2, and Phase 3 Trials  > 330Subjects Dosed  Exposure in Humans28Days   Patents to2034+    505(b)(2) Development Pathway  Studied in multiple ocular refractive indications  Nyxol  APX3330 
 

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

   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  Novel Alpha 1/2 Blocker Eye Drop for Refractive Indications (505(b)(2) Pathway)  Safety Data  Efficacy Data  Nyxol: 0.75% Phentolamine 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   
 

   Nyxol®  Phentolamine Mesylate  NVD    P  Presbyopia  RM  Night Vision Disturbances  Reversal of Mydriasis  0.4%            +   
 

 Reversal of Mydriasis (RM) – Acute Treatment   At many annual eye exams and 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 Current Commercially Available Treatments  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 Rev-Eyes (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 counteract the effect of mydriatic drugs (alpha agonists and cholinergic blockers) used to dilate the pupilConvenient and Stable 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  Seeking Treatment Findings    Patients likely to request reversal of dilation1  80%  Eye care providers likely to use reversal drops2  70%  Source: 1.GlobalData Market Research Report, 2020 – percentage includes those who answered moderately to highly likely (4-7 on a scale of 1-7) 2.GlobalData Market Research Report, 2020 – percentage includes those who answered moderately to highly likely (6-10 on a scale of 0-10)   RM 
 

   RM MIRA-2 Phase 3 Registration Design  Completed 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 sites168 target healthy subjects  Nyxol drop(s)(2 drops study eye, 1 drop fellow eye)  Mydriatic Agent A, B, or C  Placebo drop(s)(2 drops study eye, 1 drop fellow eye)  Treatment Time 0 (Max Dilation)  Primary: % of subjects (study eye) returning to baseline (within 0.2 mm) pupil diameter (PD) at 90 minSecondary:% of subjects returning to baseline at 30min, 1h, 2h, 3h, 4h, 6h, 24h (overall, by mydriatic agent, by iris color)Mean change in pupil diameter from mydriatic max at all timepoints (overall, by mydriatic agent, by iris color)Accommodation (Tropicamide/Paremyd)Safety and tolerability (redness)  Endpoints  Started and Completed Enrollment in 4Q20 – 185 Subjects  Topline Results Expected in 1Q21  Reported in March 2021  Eligibility Screening  Randomization  Mydriatic Agents 3:1:1 – 2.5% phenylephrine (alpha 1 agonist), 1% tropicamide (cholinergic blocker), Paremyd® (combination)    1:1  RM 
 

 Primary Endpoint: % of Subjects Study Eye Returning to Baseline PD at 90 Min  Source: MIRA-2 Trial, mITT Population (same as Safety Population), *Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd)  Nyxol Met the Primary & Secondary Endpoints at 90 Min; Additionally at 60 Min & All Subsequent Timepoints     Max pupil dilation, Treatment  Mydriatic  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  Nyxol Reduced More Subjects to Baseline Pupil Diameter (PD)  Nyxol Reduced PD Faster Across All Mydriatic Agents*     MIRA-2 Phase 3 Trial  *Data include all three mydriatics (Phenylephrine, Tropicamide, Paremyd)  p<0.0001  RM 
 

 Secondary Endpoint: Mean Pupil Diameter Over Time by Mydriatic Agent  Source: mITT Population, MIRA-2 Trial, Standard Error bars are shown.  Nyxol Reduced Pupil Diameter With All Mydriatic Agents; More Rapidly with Phenylephrine as Expected      MIRA-2 Phase 3 Trial  Mydriatic  Max pupil dilation, Treatment  Max pupil dilation, Treatment  Mydriatic  Nyxol More Rapidly Reduced PD in Subjects Across All 3 Mydriatic Agents   Mean Pupil Diameter  RM  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.0001     
 

   Secondary Endpoint: % of Subjects Returning to Baseline PD by Iris Color   Source: MIRA-2 Trial mITT Population,, Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd)  Evidence of Efficacy in Subjects with Either Light or Dark Irides, with a More Vigorous Response in Light Irides  MIRA-2 Phase 3 Trial  p<0.0001  p<0.0001  p<0.01  p<0.0001  p<0.0001  p<0.0001  p<0.0001  p<0.001  p<0.001  p<0.001  p<0.01  p<0.0001  Percent of Subjects Returning to ≤ 0.2 mm of Baseline by Iris Color   More Subjects Returned to PD Baseline with Nyxol in Both Light and Dark Irides   RM 
 

 Secondary Endpoint: Accommodation And Time Savings  Nyxol Demonstrates a Faster Return to Baseline Accommodation and Shorter Dilation Time by 4-5 Hours  Source: MIRA-2 CSR table #14.2.3.2.1. PP population is the per protocol population.   Note: Worsening of accommodation was defined as an amplitude decrease of greater than 1 diopter     Percent of Subjects with Unchanged Accommodation from Baseline (Tropicamide or Paremyd)Study Eye, PP population  MIRA-2 Phase 3 Trial  RM  Overall  MydriaticAgent  Irides Color  n=185  n=185  n=97  n=34  n=81  n=84  n=34  Average Time to Return to ≤ 0.2 mm of Baseline PD  Δt= 3.5 hrs  Δt= 3.2 hrs  Δt= 3.4 hrs  Δt= 4.1 hrs  Δt= 3.6 hrs  Δt= 2.3 hrs  Δt= 4.5 hrs 
 

   Summary of Positive MIRA-2 Phase 3 Results for Nyxol Eye Drops  Met primary endpoint at 90 minutes with high statistical significance with 2 drops of NyxolMet all key secondary endpoints with high statistical significanceEfficacy for all 3 mydriatic agents – phenylephrine, tropicamide, and Paremyd®  Efficacy in both light and dark iris colorsEfficacy with only one Nyxol drop in non-study eyeFavorable safety profileNo serious AEs, no drop-outs from AEs, no systemic AEs were observed in ≥ 5% of subjectsMild, transient conjunctival hyperemia reported in the first hour and declined steadily thereafter. Baseline mean of 0.7, the mean hyperemia score increased by approximately 1.0 unit on CCLRU scale  mITT Population, MIRA-2 Trial  Sustained Efficacy with a Favorable Safety Profile in Reversing Mydriasis with Nyxol  Complete a second RM Phase 3 trial with increased subjects ~330 to also meet 24-hour safety population exposureComplete RM trial with 20 subjects ages 3 to 11 per pediatric planComplete registration batches with 1-year CMC stability and make commercial batches  Path to Registration  Submit NDA by Late 2022    Proposed Indication The treatment of pharmacologically induced mydriasis produced by adrenergic (e.g. phenylephrine) or parasympatholytic (e.g. tropicamide) agents, or a combination thereof.  RM 
 

 Reversal of Mydriasis (RM) Market Opportunity  GlobalData market research reportVision Care Market Grows 2.4 Percent in 12-Months Ending September 2019. Vision Monday, January 20, 2020.  With No Commercially Available Treatment, Nyxol May Provide Significant Revenue Potential  > 65% PatientsReport moderate to severe negative impact of dilated exams1  $5 - $20Price range surveyed for cash pay per patient with room for physician markup1    $325M - $1B+Estimated US RM Market Opportunity  100M+General and specialty eye exams per year1    > $6B Eye Exam MarketExams, the third-largest category, grew faster than both prescription lenses and frames  Use of phenylephrine, tropicamide, Paremyd®, or combinations of such comprise nearly 95% of dilating eye drops used by eyecare professionals.1   OptoMap: Retinal screening for those wanting to avoid dilations but not a replacement for full dilated eye exam  $40-65 paid by patients   RM 
 

   Nyxol®  Phentolamine Mesylate  NVD    P  Presbyopia  RM  Night Vision Disturbances  Reversal of Mydriasis  0.4%            +   
 

 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 & Very Large Market  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%  ~$9-$18B Market Opportunity  Market Assumptions:Total patients - 120 million patientsPrice per month - $50Patients considering eyedrops - ~50%Refills (Months) - 3 to 6 
 

 Presbyopia – Chronic Opportunity  “Pin-hole” effect of Nyxol and low dose pilocarpine may improve near vision by enhancing depth of field 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 and daytime use of fractional concentration of pilocarpine  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  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      P 
 

 Product Profile: Nyxol ® + Low-Dose Pilocarpine (LDP) Combo  Moderate Action on Iris Dilator and Iris Sphincter Muscles for Near Vision Improvement  0.4%            0.75%Nyxol  0.4% LDP      Iris Dilator Muscle Inhibition  Iris Sphincter Muscle Activation      Phentolamine (alpha1/2 antagonist) approved non-ocular injectable indications decade(s) ago 505(b)(2)Novel MOA on iris dilator with 24+ hour durabilityModerate 1+mm pupil reductionNo daytime redness w/ chronic evening dosing NyxolWell-tolerated with no systemic effectsStable, preservative-free, single use vial  Pilocarpine (cholinergic agonist) approved decades ago Known MOA on sphincter muscle with potent miotic effects at approved doses (1%, 2%, 4%)Chronic daily dosing of LDP, a more moderate mioticLow concentration avoids known tolerability issues:headache and browacherednessaccommodative spasm causing loss of distance vision especially at night    Nyxol  LDP    1.5 to 2.5 mm PD reductionmoves toward the ‘pin-hole’ (2.0 to 2.5 mm, up to 3 mm)    Source: Nyxol® data from 8 completed trials; Pilocarpine Product label and Literature  P 
 

   Presbyopia VEGA-1 Phase 2 Design  Clinical trial NCT#04675151. DCNVA = distance-corrected near visual acuity . BCDVA = best corrected distance visual acuity   Randomized, Double-Masked, Placebo-Controlled, Multi-Center One-Week Trial  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  Visit 1    VEGA-1  Randomization  4 arms  0.75% Nyxol   Placebo  17 US sites150 presbyopic patients  Visit 2 (3 – 6 Days Later)  Screening  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  Evening Dosing(3-4 doses)  Males or females ≥ 40 and ≤ 64 years of ageBCDVA of 0.0 LogMAR(20/20 Snellen equivalent) or better in each eye under photopic conditionsDCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse in photopic conditions in each eye & binocularly  Eligibility Criteria  P  Phase 2 Enrollment Completed Feb to May 2021 – 150 Subjects Reported Topline Results End of 2Q21 
 

   Primary Endpoint: % of Subjects ≥ 15 Letter Gain in Photopic DCNVA at 1 Hour  Primary Endpoint Was Significantly Met for Nyxol + LDP Gaining ≥ 15 Letters Near Vision  VEGA-1 Phase 2 Trial  p=0.006  30% Placebo Adjusted Responders    Source: VEGA-1 TLR Table 14.2.1.2 % of Subjects With Improvement From Baseline in Photopic DCNVA by Time Point (PP Population). 15 letters is 3 lines and 10 letters is 2 lines.  Note: PP population differs from mITT by only one subject; results were essentially identical.  P 
 

 Secondary Endpoint: % of Subjects ≥ 15 Letter DCNVA Gain At All Timepoints  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.  Nyxol + LDP Had Strong Response with ≥ 15 Letter Near Gain from 30 Minutes to 6 Hours    Durable benefit over 6 hours  Rapid onset of efficacy      Similar Efficacy was Observed In:Study Eye and Fellow EyeLight and Dark Irides  P  Nyxol alone effect (~12 hr before Time 0)  VEGA-1 Phase 2 Trial   
 

 2nd Endpoint: % of Subjects ≥ 15 Letter Gain In Near & ≤ 5 Letter Loss In Distance  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)  Phase 3 Approval Endpoint Confirmed Greater Efficacy of Combo over Components at Multiple Timepoints   p=0.0009  Statistics Compared to Nyxol+LDP armPowered for comparison to placebo whereas comparison to component arms were designed to inform the Phase 3 sample size    VEGA-1 Phase 2 Trial  P  Even with a small sample size, combination arm provided statistically meaningful results at 30 min and 2 hours vs. LDP and Nyxol alone arms  
 

 Secondary Endpoint: Mean Pupil Diameter Over Time  Source: VEGA-1 TLR Table 14.2.12.1 Observed Values and Change from Baseline in Photopic Pupil Diameter by Time Point (PP Population)   Achieved Pupil Size ~2mm in Nyxol+LDP Consistent with 3-line Improvement in Near Vision  Nyxol+LDP arm statistically significant compared to all arms   **p<0.01***p<0.0001    VEGA-1 Phase 2 Trial  P 
 

 Secondary Endpoint: Safety Findings   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)   Nyxol+LDP Combination Was Well Tolerated with a Favorable Safety Profile  ​  Placebo Alonen=45  Nyxol Alonen=30  LDP Alonen=31  Nyxol+LDPn=44  Total Treatment Emergent Adverse Events (n)​  4  18  13  50  TEAEs by Severity (n [%])​Mild​Moderate​Severe​  ​1 (2.2%)​1 (2.2%)​0 (0%)​  6 (20%)​0 (0%)​0 (0%)​  6 (19.4%)​0 (0%)​0 (0%)​  ​13 (29.5%)​1 (2.3%)​1 (2.3%)​  AEs Occurring in ≥ 5% of subjects (n [%])​Instillation Site Pain (Mild)Instillation Site Erythema (Mild)​Conjunctival Hyperemia (Mild)Eye Disorders (Mild)​  ​1 (2.2%)​0 (0%)0 (0%)​1 (2.2%)  3 (10%)​3 (10%)2 (6.7%)​2 (6.7%)  0 (0%)​2 (6.5%)0 (0%)​4 (12.9%)  ​4 (9.1%)5 (11.4%)​2 (4.5%)​5 (11.4%)     No deaths, no serious AEs Almost all AEs were mild0% headaches or brow aches reported for Nyxol+LDP arm≤ 5% mild, transient conjunctival hyperemia AEs in Nyxol+LDP armDistance vision: 100% Nyxol + LDP arm had ≤ 5 letter distance loss in photopic lighting (95% in mesopic)No change in IOP    Conjunctival Hyperemia CCLRU Scale for Reference    Nyxol + LDP and LDP alone Only transient 0.5 point mean increase  P 
 

 Product Attributes*  Nyxol+LDP compared to market leader  Efficacy (all time-points)  ✓+  Safety: Maintain Distance Vision (especially at night)  ✓+  Safety: Tolerability (no headaches)  ✓+  Durability (at least 6 hours)  ✓+  Fast Onset (within 30 mins)  ✓+  Convenience (daily drops)  ✓  Tunable Pupil Modulation  ✓+  ASCRS (July 2021) Abstract# 76645 (Phase 2) and 74336 (Phase 3)✓+- Indicates better compared to market leader✓- Indicates comparable to market leader  Potential ‘Best in Class’ Presbyopia Drop  Nyxol+LDP Combination Outperforms Market Leader in Efficacy, Safety, Durability and Onset  Gemini I Phase 3: AGN-190584 Provides Rapid Improvement of Distance Corrected Near Vision That Is Maintained in Participants with Presbyopia- ASCRS 2021 Presentation  Gemini I Phase 3: Safety and Efficacy of AGN-190584 in Participants with Presbyopia- ASCRS Abstract# 74336  Phase 2 Clinical Trial To Evaluate The Efficacy of Phentolamine Ophthalmic Solution And Low-Dose Pilocarpine For The Treatment of Presbyopia- ASCRS Abstract# 76645 
 

         Phase 3  Phase 2  Phase 1  Presbyopia Eye Drops Competitive Landscape  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)  Lenz(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  Ocuphire is differentiated by using both the dilator and sphincter muscles moderately to reach a pin-hole pupil size  Presbyopia Next Steps:Advance into Phase 3 Registration Trials in 2022; Towards a Potential NDA in 2023 
 

   Nyxol®  Phentolamine Mesylate  NVD    P  Presbyopia  RM  Night Vision Disturbances  Reversal of Mydriasis  0.4%            +   
 

 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  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 
 

     NVD LYNX-1 Phase 3 Registration Design  Ongoing 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  Phase 3 Initiated in Late 4Q20  Top Line Expected Early 2022    NVD 
 

     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  Percent of Subject Eyes  p=0.029  p=0.04  p=0.16    Baseline Pupil Diameter: Placebo 4.6mm, Nyxol 4.7mm  *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  p = 0.0002  p = 0.0001  p = 0.0004  NVD 
 

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

 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 
 

   APX3330 History and Ref-1 Inhibition Mechanism  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  DR  DME 
 

 APX3330 Down-Regulates VEGF Protein and Anti-Inflammatory Cytokines   In Vivo and In Vitro Evidence of APX Dual Pathway Mechanism of Action  Treatment of APX3330 (10mg/kg, oral gavage) in rats with type 1 diabetes and induced stroke shows a significant decrease of VEGF signaling. Increased VEGF is a hallmark of uncontrolled neovascularization and inflammation in diabetic retinopathies; current approved treatments successfully decrease VEGF levels in the eye.  Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018Apurinic/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    In vitro APX3330 suppresses pro-inflammatory cytokines in LPS stimulated murine macrophage cell lines known to be involved in macular degeneration:TNF-α is a potent cytokine that enhances secretion of VEGF-A and VEGF-B by human choroidal fibroblast cells. J Cell Physiol. 2011Genetic ablation of IL-6 led to significant suppression of AMD (murine CNV model). Am J Pathol. 2007  APX3330 Reduces VEGF Protein in the Brain of Preclinical Models  APX3330 Reduces Pro-inflammatory Cytokines in Murine Cell Lines Involved in Macular Degeneration  DR  DME 
 

 APX3330 Generally Well Tolerated with Clinical Signals  1. 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  Observations from Pre-Clinical Studies and 11 Clinical Trials of APX3330  DR  DME  Lesion Size and Corresponding Fluorescent Stains in L-CNV Models Treated with APX3330 at 25 mg/kg oral gavage  -55%    L-CNV Mouse Retina Model   APX3330 Reduces Neovascularization Similar to Eylea in Preclinical Models  Silva et al, 2021              Vehicle  25 mg/kg  50 mg/kg  APX3330 Gavage OCTLesion Volume  Human Pharmacokinetics of APX3330 at 120 mg/day     Phase 1 Clinical Trials  Human Drug Exposure Multiple Times Higher than Mouse Efficacious Levels  Human 120 mg/day  Mice 25 mg/kg  Source: Unpublished Data  300 mg BID (600 mg/day total) dosing strategy for APX3330 is predicted to reach retinal AUC concentrations of 15.4 μg/mL; Significant APX3330 reaches human retina, folds greater than mice who were given APX3330 25 mg/kg (actual 2hr conc. in retina 0.1 μg/mL)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 Effects~1% Mild Gastrointestinal (diarrhea)~1% 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   Twice a day dosing of APX3330 being developed to providesteady state effectiveness with a tolerable chronic safety profile    DR  DME 
 

   DR/DME ZETA-1 Phase 2 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)  Ongoing, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar to Eylea P3 for Approval)    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 Initiated in April 2021  Top Line Expected in 2022 
 

 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 
 

 Boards and Milestones   
 

   Richard Lindstrom, MDUniversity of Minnesota  Ed Holland, MDLoyola University Chicago  Jay Pepose, MD, PhDUCLA  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/NyxolPast MAB Member  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 Drug Development, M&A/Financings, and Ophthalmology          Sean Ainsworth, MBALead Independent Director, Board Director ​  James Manuso, PhD/MBABoard Director​  Jay Pepose, MD, PhDBoard Director    Richard Rodgers, MBABoard Director     Susan Benton, MBABoard Director​    Cam Gallagher, MBAChair, Board Director    Mina Sooch, MBAVice-Chair, Board Director President & CEO 
 

   2021 to 2022 Ocuphire Cadence of Milestones  Multiple Data Catalysts On Path To NDA(s)  Ongoing partnering discussions with leading ophthalmic companies (including European and Asian players)  Completion of APX3330 LicenseARVO 2020 Presentation for MIRA-1 & ORION-1FDA EOP2 Meeting May 2020Completion of Transaction (Nasdaq: OCUP) and concurrent $20M financingInitiate Phase 3 RM TrialInitiate Phase 3 NVD TrialComplete Nyxol Market ResearchJournal Publications  Enrollment of Phase 3 RM TrialInitiate Phase 2 Presbyopia TrialReport Positive Phase 3 Data for RMInitiate Phase 2 DR/DME TrialEnrollment of Phase 2 Presbyopia TrialNew Patent ClaimsClosed $15M registered direct offeringReport Positive Phase 2 Data for Presbyopia  ASCRS 2021 Presentation for MIRA-2 & VEGA-1Initiate 2nd P3 RM and Pediatric RM trial for NDAEnrollment of Phase 3 NVD TrialEnrollment of Phase 2 DR/DME TrialIndustry Conferences & PublicationsManufacture 3xRegistration Batches for Nyxol Blow-Fill-Seal (BFS) Eye DropsComplete 6-month Rabbit Tox Study  Report Phase 3 Data for NVD Report 2nd Ph3 RM Trial Report Pediatric RM trial Initiate 2 Phase 3 Presbyopia TrialsReport Phase 2 Data for DR/DMEInitiate Chronic Ph3 Safety Trial (Nyxol /LDP)Complete 1 year CMC stability on 3xreg batchesSubmit Nyxol NDA filing for RM in late 2022 Manufacture Commercial Batches of Nyxol Eye Drop  2020  1H 2021  2H 2021  2022*  2023*  Report Phase 3 Data for Presbyopia TrialsPotential NDA for Nyxol in RMPotential Commercial Launch of Nyxol in USSubmit NDA filing for Nyxol for Presbyopia in 2023  *Additional Studies for NVD and DR based on Data Readouts 
 

 OCUP – Market Snapshot   Source: FactSet  Sufficient Cash Runway Into Late 2022 and Substantial Trading Liquidity  Ticker  OCUP    Price  $4.89  As of 8-10-21  Market Cap  $82 M  As of 8-10-21  Primary/FD Shares  16.9 M / 18.6 M  As of 6-30-21  Cash  $24.2 M  As of 6-30-21  Cash Runway  Into Late 2022  Guidance as of 6-30-21  Average Daily Volume  930,341  Month-to-date at 8-10-21  Short Interest  1.1%  As % of float; as of 7-31-21  Research Analyst Coverage on OCUP    James Molloy  Alliance Global Partners  John Newman  Canaccord Genuity  Kristen Kluska  Cantor Fitzgerald  Prakhar Agrawal  Jones Trading 
 

 www.ocuphire.comir@ocuphire.com    
 

 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