Form: 8-K

Current report filing

January 5, 2022


Exhibit 99.2

 Ocuphire Corporate Presentation  Mina Sooch CEO  January 5, 2022  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 you are 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 
 

   Differentiated, Late-Stage Pipeline Targeting Large Unmet Ophthalmic Markets Of The Front And Back Of The EyeNyxol with > 330 patients treated across 9 trials (505(b)(2) regulatory pathway)APX3330 with > 340 patients treated across 11 trials (NCE development pathway)Nyxol and APX3330 achieved promising clinical data and favorable safety profile across multiple Phase 1, 2, and 3 trialsPoised For Commercial SuccessAddressing 4 large markets with unmet needs: RM, Presbyopia, NVD and DR/DMESuccessful trial execution with 2 recent positive Phase 3 & Phase 2 data read-outs for Nyxol in RM and Nyxol + LDP Presbyopia, respectivelyStable, small-molecule drugs with commercial scalabilityRobust and growing IP portfolio: US and global issued thru 2034 for both assets as well as new 2039 Nyxol patent issued for presbyopiaMultiple Value Creation Opportunities With A Capital-efficient Plan$24.5 million cash reported at 12-31-21 sufficient for operations into 2Q 2023Lower-cost, fast-enrolling, shorter-duration clinical trialsFavorable, precedent regulatory environment for ophthalmic drug approvalAnalyst coverage by Cantor, Canaccord, Jones Trading, Alliance Global, and HCW  A Look Ahead Into 2022:Nyxol MIRA-3 trial for RM EARLY 2022Nyxol Pediatric trial for RM EARLY 2022Nyxol LYNX-1 trial for NVD EARLY 2022APX3330 ZETA-1 trial for DR/DME 2H22    Ocuphire PharmaNasdaq: OCUP  RM = Reversal of Mydriasis NVD = Night Vision DisturbancesDR/DME = Diabetic Retinopathy/Diabetic Macular Edema   3 
 

 Large Unmet Opportunities For The Aging Eye  Nyxol To Treat Front Of The Eye And APX3330 For The Back Of The Eye Diseases           Nyxol®  $9B - $18B   $325M - $1B  $2B - $4B  $3B - $7B  $1B - $3B  APX3330   128 MPatients  100 MPatients  16 MPatients  Presbyopia  Reversal of Mydriasis   Night Vision Disturbances  Diabetic Retinopathy  Diabetic Macular Edema  Presbyopia    10 MPatientsTotal  US Market Opportunity  US Market Opportunity  US Market Opportunity  US Market Opportunity  US Market Opportunity  Refractive  Retina  Source: GlobalData Market Research Report, 2020; Company Estimates for Market Size       
 

   Ocuphire Pipeline & Clinical Milestones  Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution)  Product Candidate  Indication  Pre-clinical  Phase 1  Phase 2  Phase 3  RegulatoryApproval  Anticipated Milestones  0.75% Nyxol®Eye Drop  Reversal of Mydriasis (RM)             MIRA-3 Phase 3 data expected in early 2022 (n=330)MIRA-4 Pediatric safety study data expected in early 2022 (n=20)  0.75% Nyxol® + Low-Dose 0.4% Pilocarpine Eye Drops  Presbyopia (P)            VEGA Phase 3 program initiated in 1H22 (n=300x2)  0.75% Nyxol®Eye Drop  Dim Light or Night Vision Disturbances (NVD)            LYNX-1 Phase 3 data expected in early 2022 (n=140)  APX3330 Oral Pill  Diabetic Retinopathy (DR)/ Macular Edema (DME)            ZETA-1Phase 2 data expected in 2H22 (n=90)  APX2009 (Intravitreal or Local Delivery)  DME or Wet Age-Related Macular Degeneration (wAMD)            Seeking partner funding for IND enabling studies and further development            Multiple Phase 3 & Phase 2 Clinical Data Readouts Anticipated Over The Next Year 
 

   6  RM  Reversal of Mydriasis    P      NVD  Presbyopia  Night Vision Disturbance  0.4%            +    Nyxol®Eye Drops 
 

     Nyxol MOA & History    Phentolamine Mesylate Reformulated As A Proprietary Topical Eye Drop  Nyxol  Phentolamine Mesylate is Active Ingredient in Nyxol: α1 & α2 Antagonist  Blocking α1Reduces Pupil Size  Blocking α1Dilates Blood Vessels  Phentolamine mesylate is currently approved for 2 indications:Regitine® (Pheochromocytoma) – intravenous injection approved in 1952OraVerse® (Reversal of oral anesthesia) – intramuscular injection approved in 2008  505(b)(2) Regulatory Approval Pathway  Nyxol blocks α1 receptors on the Iris Dilator Muscle↓Decreases Pupil Size (Moderate Miosis)      Iris Dilator Muscle   Iris Sphincter Muscle   9Phase 1, Phase 2, and Phase 3 Trials  > 330Subjects Dosed  Exposure in Humans28Days   Patent Coverage2034+ 
 

 Nyxol Improves Vision by Decreasing Pupil Size↑ Near & Distance Visual Acuity↑ Contrast Sensitivity (night)  No Systemic EffectsNo Changes in Blood PressureNo Changes in Heart RateWell-Tolerated Topical EffectsMild, Transient, Reversible Eye RednessIOP Unchanged or DecreasedNo Headaches Favorable safety profile vs competitors  Nyxol Product Candidate Profile  Nyxol Clinical Trials   Novel, Differentiated Alpha 1/2 Blocker Eye Drop For Refractive Indications  Favorable Safety Profile  Effective  Nyxol: 0.75% Phentolamine Ophthalmic SolutionPreservative Free, EDTA Free, and Stable  Effects Last ≥ 24 HoursChronic daily dosing of Nyxol at bedtime reduced pupil size for up to 24 - 36 hoursWith nighttime use, patients wake up without eye redness  Durable 
 

   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, Age 51  RM  9    Nyxol®forReversal of Mydriasis (RM) 
 

 Reversal Of Mydriasis (RM) Market Opportunity  With No Commercially Available Treatment, Nyxol May Achieve Significant Revenue Potential  > 65% of PatientsReport moderate to severe negative impact of dilated exams1  $10 - $20Price range for cash pay per patient with room for physician markup1    100M+General and specialty eye exams per year1  GlobalData Market Research ReportGlobalData Market Research Report, 2020 – percentage includes those who answered moderately to highly likely (4-7 on a scale of 1-7).GlobalData Market Research Report, 2020 – percentage includes those who answered moderately to highly likely (6-10 on a scale of 0-10)  Nyxol ‘s MOA has a minimal side effect profile (unlike cholinergic agonists such as pilocarpine)  $325M - $1BEstimated US RM Market Opportunity  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  80% of PatientsLikely to request a reversal of dilation drop2    The Problem  95% of Dilating DropsUsed by Eye Care Providers were used in MIRA Clinical Trials1    No Current Commercially Available Treatments  RM 
 

   MIRA-2/3 Phase 3 Registration Trial Design  Randomized, Double-Masked, Placebo-Controlled, Parallel, One-Day Trial  Mydriasis-1 Hour  1:1  Mydriatic Agent A, B, or C  0.75% Nyxol   Placebo  12 to 16 US sites185 to 330target 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)  Primary: % of subjects (study eye) returning to baseline (within 0.2 mm) photopic pupil diameter (PD) at 90 minSecondary:% of subjects returning to baseline at 0min, 30min, 1h, 90 min 2h, 3h, 4h, 6h, 24h (overall, by mydriatic agent, by iris color)Mean change in pupil diameter at all timepoints Accommodation (Tropicamide/Paremyd)Visual Acuity with Glare (new) Pupillary Light Reflex (new)Safety and tolerability (redness)  Endpoints  Enrollment MIRA-3 Started in 4Q21  Topline Results Expected in Early 2022  Eligibility Screening  Randomization    1:12:1           Treatment (Max Dilation)0 min  30min  1 Hr  90min    2 Hr    3 Hr    4 Hr     6 Hr     24 Hr  Primary Endpoint  Follow Up Visit  Mydriatic Agents 3:1:1 – 2.5% phenylephrine (alpha-1 agonist), 1% tropicamide (cholinergic blocker), Paremyd® (combination)     RM 
 

 MIRA-2 RM Phase 3 Trial Met Primary & Secondary Endpoints  Source: MIRA-2 Trial, mITT Population (same as Safety Population), *Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd)  49% Of Patients Returned To < 0.2mm Of Baseline At 90mins Vs. 7% Placebo    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 
 

 Summary Of Positive MIRA-2 Phase 3 Results For Nyxol Eye Drops  mITT Population, MIRA-2 Trial  Rapid Efficacy With A Favorable Safety Profile In Reversing Mydriasis With Nyxol      No 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      Efficacy    Safety    Met primary endpoint at 90 minutes with high statistical significance with 2 and 1 drop of NyxolMet all key secondary endpoints with high statistical significanceNyxol more rapidly reduced PD across all 3 mydriatic agents - phenylephrine, tropicamide, and Paremyd®  More subjects returned to PD baseline with Nyxol in both light and dark irides Nyxol demonstrated a faster return to baseline accommodationNyxol reduced the dilation time by ~4 hrs           RM   
 

 NDA Submission Targeted In Late 2022    Ongoing Activities Sets Ocuphire On Path To A Potential Regulatory Approval In 2023    Complete RM trial with 20 subjects ages 3 to 11 per agreed FDA initial pediatric plan  Pediatric Safety  Complete a 2nd Phase 3 trial in RM with ~330 subjects which also meets 24-hour safety population exposure  P3 Clinical Trial  Complete 3 registration batches on 1-year CMC stability  Manufacturing  Submit NDA by Late 2022  Regulatory Approval                          Nyxol®  Target Label Indication The treatment of pharmacologically induced mydriasis produced by adrenergic (e.g. phenylephrine) or parasympatholytic (e.g. tropicamide) agents, or a combination thereof.    RM  5 single unit dose vials pack 
 

    Pre-Commercial & Go-To-Market Strategy  Activities Underway To Support Capital-Efficient Nyxol RM Commercial Launch    Brand Awareness Across Eye Care Professionals  PhysicianTargeting    Patient Journey  Market Development    Engage leading Key Opinion Leaders and Professional Societies to establish OCUP as an emerging company to address unmet needs in the front and back of the eye disorders   Establish Ocuphire as a patient-centric company and leader in ocular health through education and patient access programs (also using digital and social media marketing)  Conduct HCP segmentation and targeting to drive early adoption and capture post-market data and patient experience  Initiate branded and unbranded education for ophthalmologists, optometrists and practice professionals  Eye Care Practitioners in U.S.  ​  Total Retina Specialists​  3,000​  Total Optometrists​  46,000​  Total Ophthalmologists​  20,000​     OcuphireGo-To Market  Evaluating commercial sales and distribution partner(s)  ASRS; AMA; AAO; Women in Optometry (WO); AOA Excel and Jobson Medical Information  RM 
 

     P  16  Nyxol® forPRESBYOPIA  “By Age 45, 80% of Americans will struggle with Presbyopia, and by age 50, nearly everyone will.” NY Times   
 

 2021: The Time For Presbyopia Drops  Sources: Academic review articles, journals, and publications   Headlines From Academia And Industry Articles Thru The Year With An Early First Approval  “The correction of presbyopia remains ophthalmology’s ‘Holy Grail’…”-OIS  10/29/2021  P 
 

 Presbyopia Is A Burgeoning Opportunity   Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, Cataract & Refractive Surgery Today, 2021, NEI 2010 data.Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday.   Large Market Being Developed, Pupil Modulation Eye Drops May Replace Reading Glasses   ~$9B - $18B Estimated US Presbyopia Market Opportunity  VUITY™ is the only FDA approved Eye Drop, Launched in Dec 2021Significant room for improvement for new entrants with better product attributes in a newly developed presbyopia eye drop market  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  The Problem  3-6 refills per year    Private Cash Pay(Vuity $79/refill List Price)    More Likely to Use Eye Drops  No refractive error/ never worn glasses  Cataract surgery for artificial lens  Poor near vision (any age)  Poor distance vision     50% would use eye drop (37 M)  P  >$35B 
 

 Product Profile: Nyxol ® + Low-Dose Pilocarpine (LDP) Combo  Source: 1) Nyxol® data from 9 completed trials; Pilocarpine Product label and Literature  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)Novel MOA on iris dilator with 24+ hour durabilityModerate 1+mm pupil reductionNo daytime redness Well-tolerated with no systemic effectsStable, preservative-free, single-use vial  Pilocarpine (cholinergic agonist)Known MOA on sphincter muscle with potent miotic effects at approved doses (1%, 2%, 4%)Low concentration avoids known tolerability issues:headache and browacherednessaccommodative spasm causing loss of distance vision especially at night    1.5 to 2.5 mm PD reduction moves toward the pin-hole (2 to 2.5 mm, up to 3 mm)  Daytime drop  Evening drop    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 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 
 

 VEGA-1 Phase 2 Trial Met Primary & Secondary Endpoints  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    VEGA-1 Phase 2 Trial  Durable benefit over 6 hours  Rapid onset of efficacy      Nyxol alone effect (~12 hr data)      Primary Endpoint  P  Note: PP population differs from mITT by only one subject; results were essentially identical. 
 

   Secondary Endpoints: Improved DCNVA Without BCDVA Loss  Source: VEGA-1 TLR Table 14.2.2.2 Percent of Subjects with >= 15 Letters of Improvement in Photopic DCNVA and < 5 Letters of Loss in Photopic Binocular BCDVA by Time Point (PP Population); Table 14.2.1.2 Percent of Subjects With Improvement From Baseline in Photopic DCNVA by Time Point   Pre-Specified Endpoints Further Demonstrate Nyxol’s Component Efficacy & 10 Letter Effects  VEGA-1 Phase 2 Trial  P  p=0.015  p=0.015  p=0.03  p=0.008  Even with a small sample size, combination arm provided statistically meaningful results vs. LDP and Nyxol alone arms   * Trend seen at other assessed timepoints 
 

 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 
 

 Summary Of Positive VEGA-1 Phase 2 Results   PP Population, VEGA-1 Trial  Nyxol + LDP Had Strong Efficacy Response & Well Tolerated Safety Profile           Efficacy    Safety    Met primary endpoint with statistical significance at 1 hour with Nyxol® plus Low-Dose Pilocarpine (LDP)Met key secondary endpoints with statistical significanceGained 15 letters (3 lines) in near vision with less than 5 letters of distance vision loss at all timepoints vs. placebo and select timepoints for componentsRapid onset of efficacy within 30 minsDurable near vision improvement through at least 6 hoursSustained significant reduction in pupil diameter for at least 18 hoursNear vision efficacy seen both monocularly and binocularlyEfficacy in both light and dark irides        P    No serious AEs, almost all AEs were mildNo headaches, no brow aches, and no blurry vision AEs were reportedNo material change in distance vision under photopic and mesopic lightingNo change in IOPMild, transient conjunctival hyperemia (eye redness) observed in <5% of subjects 
 

 Potential ‘Best in Class’ Presbyopia Drop  Product Attributes*  Nyxol+LDP  VUITYTM  1) Efficacy (3 Line Gain in DCNVA - Primary Endpoint Responders)  61%  26-31%  2a) Safety: Loss of Distance in Mesopic  None  None  2b) Safety: Tolerability  No Headaches  >5% Headaches  2c) Safety: Conjunctival Hyperemia  <5% redness  >5% redness  3) Durability (responders at 6 hours)  37%  18%  4) Fast Onset (responders at 30 mins)  61%  35%  *Differences in cross trial comparisons are not necessarily statistically significant. Nyxol Data: ASCRS (July 2021) Abstract# 76645 (Phase 2) and 74336 (Phase 3). VUITYTM Data: FDA Label and AAO 2021 Presentation.  Nyxol+LDP Combination Data Outperforms In Efficacy, Safety, Durability And Onset  P  Nyxol’s Potential Differentiated Solution 
 

           Phase 2  Phase 1  Presbyopia Eye Drops Competitive Landscape  Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020  Pupil modulation MOA    Combination drugs      Soften lens MOA          Phase 3  Phase 2  Phase 1  Allergan(VUITYTM;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*    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  Nyxol Next Steps  Validation of Pupil Modulating Drops Achieving Pin-Hole Effect & Efficacy, Many With Pilocarpine  Advance into Phase 3 Presbyopia Registration Trials (1H22)↓Potential NDA Submission(2023)  P 
 

     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, Age 42  Nyxol® forDim Light or Night Vision Disturbances  27  NVD 
 

 Market Opportunity In Dim Light Or Night Vision Disturbances  No Approved Treatments With Ripe Opportunity For Growth   No Approved Treatments  $2B - $4BEstimated US NVD Market 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  The Problem  Seeking Treatment Findings    Patients willing to try a new eye drop treatment  67%       NVD  Pupil reduction with Nyxol may offer a potential solution to peripheral optical imperfections  After  Before  Source: GlobalData Market Research Report, 2020 
 

     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  20 US sites140 - 160 patients with NVD  Phase 3 Initiated in Late 4Q20  Top Line Expected Early 2022  NVD  Day 0      Day 8Assessments  Primary Endpoint  Day 15Assessments   
 

     ORION-1 Phase 2 Trial  NYX-SNV Phase 2 Trial    Nyxol Demonstrated Clinical Effect In 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  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  p = 0.0002  p = 0.0001  p = 0.0004  NVD 
 

     DR  DME    31      Diabetic Retinopathy  Diabetic Macular Edema  Apx3330tablets 
 

 Large, Unmet Need in Diabetic Eye Diseases (US)    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 worldwideDiabetes damages small blood vessels within the eye causing leakage, oxygen starvation, and abnormal vessel growthDR patients are not routinely treated with approved injectable anti-VEGF drugsDR progresses resulting in vision lossCurrent treatment for DME are not satisfactory 25% non-responders50% 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  Oral Alternatives To Injectable Therapies Are Needed For Earlier Stages Of Disease  DR  DME  DR  DME  $3B - $7BEstimated US DR Market Opportunity  $1B - $3BEstimated US DME Market Opportunity    Limited Retinal Treatment Options for Diabetic Patients 
 

 APX3330: Drug Development History And Patents    Significant Preclinical & Clinical Data Supporting Human Safety, MOA, and PK  11Phase 1 & Phase 2 Trials  >340Subjects Dosed  Exposure in Humans 365 Days   Patent Coverage 2034+    Studied in inflammation/hepatitis & cancer patients (Studied by Eisai & Apexian, respectively)  APX3330New Chemical Entity  Preclinical Efficacy & Toxicology Package  APX3330IND  6 Phase 1 Trials  5 Phase 2 Trials  Phase 2b Trials   Phase 3Registration  NDA Filing        Focus on Ophthalmology    DR  DME 
 

   APX3330 History And Ref-1 Inhibition Mechanism  Logsdon et al (2018), Li et al (2014).  Ref-1 Involved In Multiple 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-αChemokines  Neovascularization  Lucentis®EYLEA®  Anti-VEGF    Steroids    APX3330  Ref-1 (reduction-oxidation effector factor-1) is a novel target discovered by Dr. Mark R. Kelley at Indiana University School of MedicineAPX3330 is a small molecule oral drug candidate and a first-in-class inhibitor of Ref-1APX3330 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   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 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.    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 
 

 Preclinical Data: Oral APX3330 Blocks Neovascularization  - 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- Published data on EYLEA  Lesion Volume Decrease With Oral APX3330 In Murine Laser CNV Model Similar To EYLEA® Data      -44%  EYLEA  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   Silva et al, 2021              Vehicle  25 mg/kg  50 mg/kg  APX3330 Gavage OCTLesion Volume    L-CNV Mouse Retina Model   APX3330  DR  DME 
 

 Phase 1/2 Clinical Trials: PK Data Supporting The ZETA-1 Trial  Apexian preclinical dataEisai preclinical dataSilva 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  APX3330 Is Bioavailable And Reaches The Retina Via Oral Administration    Human Pharmacokinetics of APX3330 at 120 mg/day     Phase 1 PK Clinical Data  Human Drug Exposure Multiple Times Higher than Mouse Efficacious Levels  Human 120 mg/day  Mice 25 mg/kg  Source: Eisai/Apexian Human PK data  Human  Mouse  Rat  10 mg/kg APX3330 oral gavage measured in rat eye2  Established PBPK model predicts APX3330 reaches sufficient human retinal concentrations3  300 mg BID (600 mg/day total)  25 mg/kg APX3330 oral gavage measured in mouse retina1  Does oral administration of APX3330 reach the retina in sufficient concentration?  DR  DME 
 

 Improving Eye Health in Diabetics ↓ Inflammation ↓ Abnormal AngiogenesisEnhance Compliance & ExposureOral pill may reduce the burden of frequent anti-VEGF injections  Few Systemic Adverse Effects< 5% Mild Gastrointestinal (diarrhea)< 5% Mild Skin Rash (reversible)Lack of Significant Acute Neurologic, Cardiovascular, Liver, or Pulmonary toxicityNo Ocular EffectsNo observed ocular AEs  APX3330 Product Candidate Profile For Multiple Retinal Indications     First-In-Class Ref-1 Inhibitor With Favorable Human Safety Data  APX3330: Well-tolerated Oral Dose up to 600mg/dayTwice Daily Dosing  DR  DME  Expected Efficacy Data  Favorable Safety Profile 
 

   DR/DME ZETA-1 Phase 2b 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 Pivotal DR P3)  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)DRSS change at week 12Rescue subjectsSafety and tolerabilityExploratory:Labs / PK  Endpoints  Phase 2b Start Initiated in April 2021  Top Line Expected in 2022  DR  DME  ZETA-1  Eligibility Screening  Randomization  APX3330 600mg/day (BID)  Placebo BID    24 US sites~100 participants with moderate-to-severe NPDR or mild PDRNoncentral DME is permitted    1:1  Week 0      Week 12  Week 24      Week 4  Primary Endpoint 
 

 Innovative Approach For Retinal Diseases With APX Platform   Potential First Oral Rx for Retina DiseasesFirst-line earlier intervention for the diabetic eye Add-on therapy to current anti-VEGF treatmentsProven Novel MechanismMay decrease both inflammation and angiogenesisConvenient Daily RegimenFavorable Oral Safety Profile As seen in 11 completed Phase 1 and Phase 2 clinical trialsImprove Patient Compliance Potentially alleviate the frequent burden of injections    Potential Differentiated Solution  APX3330 May Treat Patients Across The Spectrum Of Retinal Diseases  APX3330  Current anti-VEGF treatments  APX2009APX2014APX3330(Local Delivery)    DR  DME 
 

 Team/Boards, Milestones, And Financial Data 
 

 Ocuphire Management Team  Decades Of Biotech And Drug Development Experience    Mina Sooch, MBAPresident & CEO and Founder    Drey ColemanVP, Clinical Operations    Amy Rabourn, CPAVP, Finance    Charlie Hoffmann, MBAVP Corporate Development and Operations    Mitch Brigell, PhDHead, Clinical Development and Strategy    Daniela Oniciu​, PhDGlobal Head, R&D, Chemistryand Product Development      Ronil Patel, MSSenior Director BD and Market Strategy    Chris ErnstGlobal Head, QAand Manufacturing    Barbara Withers, PhDVP, Clinical and Regulatory Strategy 
 

 Ocuphire's World-Class Medical Advisory Board  Fortunate For The Insights Of Leading KOLs & Drug Candidate Co-Founders  James Katz, MDUniversity of Illinois  Jay Pepose, MD, PhDUCLA  Thomas Samuelson, MDUniversity of Minnesota   Paul Karpecki, ODIndiana University  Eliot Lazar, MDGeorgetown University  Marguerite McDonald, MDColumbia University  David Boyer, MDChicago Medical School   Mark Kelley, PhDIndiana UniversityCo-Founder Apexian/APX3330  elCON Medical  Michael Allingham, MD, PhDUniversity of North Carolina  Peter Kaiser, MDHarvard Medical School  Jeffrey Heier, MDBoston University   Y. Ralph Chu, MDNorthwestern University  Douglas Devries, ODUniversity of Nevada  David Brown, MDBaylor University  Mitch Jackson, MDChicago Medical School  Ed Holland, MDLoyola University Chicago  Jack Holladay, MDUniversity of Texas  David Lally, MDVanderbilt University 
 

 Ocuphire Board of Directors           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  Seasoned Directors With Decades Of Drug Development, M&A/Financings, And Ophthalmology 
 

 45        Ocuphire Cadence Of MilestonesMultiple Data Catalysts On Path To NDA(s)  Ongoing Partnering Discussions with Leading Ophthalmic Companies (including European and Asian Players)  2021      2022          Report 2nd Phase 3 Data for RM        Report Pediatric Data in RM        Report Phase 3 Data for NVD        Submit Nyxol NDA for RM        Report Phase 2 Data for DR/DME        Initiate Two Phase 3 Presbyopia Trials            Report Positive Phase 3 Data for RM (MIRA-2)  Report Positive Phase 2 Data for Presbyopia (VEGA-1)  New Patent Claims for Presbyopia  ASCRS 2021 Presentation for MIRA-2 & VEGA-1  Manufacture 3xRegistration Batches for Nyxol Blow-Fill- Seal (BFS) Eye Drops  Initiate 2nd Phase 3 RM and Pediatric RM trial Initiate Phase 3 Chronic Safety Trial  Early 2022 
 

   Ophthalmology – An Attractive Biotech Sector   FavorableRegulatoryEnvironment   Source:1.Endpoint Dec 29, 2021- Hitting a new record on drug approvals, the FDA offers a thumbs-up to another atopic dermatitis contender; OIS Year in Review 2021; Company press releases  Deal Activity And FDA Approvals In Ophthalmology In 2021  New Product Approvals  *sNDA  ~$2B  ~$1.5B  $1.75B  7 of 60 Total FDA Drug Approvals in 2021 Were Ophthalmic Drugs1     AgingPopulation   Ranibizumab biosimilar    ActiveM&A  April 2021  October 2021  December 2021  December 2021  September 2021    Lower Cost,Quick Enrolling,Short Duration Clinical Trials  Deal Activity 
 

 OCUP – Market Snapshot   Source: FactSet  Active Trading Volume And Sufficient Cash Runway Through 2Q 2023   Ticker  OCUP    Price  $3.73  As of 12-31-21  Market Cap  $64.8 M  As of 12-31-21  Shares Outstanding  18.8 M   As of 12-31-21  Cash  $24.5 M  As of 12-31-21 (unaudited)  Cash Runway  Sufficient into 2Q 2023  Guidance as of 1-5-22  Average Daily Volume  390 K  As of 12-31-21 (Dec. Avg)  Short Interest  868 K; 5.1% of Float  As of 12-15-21  Research Analyst Coverage on OCUP    John Newman  Canaccord Genuity  Kristen Kluska  Cantor Fitzgerald  James Molloy  Alliance Global Partners  Prakhar Agrawal  Jones Trading  Matthew Caufield  H. C. Wainwright 
 

 www.ocuphire.comir@ocuphire.com  Ocuphire Pharma 
 

 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