Form: 8-K

Current report filing

August 12, 2022


Exhibit 99.2

 Ocuphire Corporate Presentation  August 2022 
 

 Disclosures and Forward-Looking Statements   This presentation contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements concerning the success and timing of planned regulatory filings, including planned NDA filings, pre-commercial activities, commercialization strategy and timelines, business strategy, product labels, cash runway, scalability, future clinical trials in reversal of mydriasis (RM), presbyopia (P), dim light/night vision disturbance (NVD) and diabetic retinopathy (DR)/diabetic macular edema (DME), including the potential for Nyxol to be a “best in class” presbyopia drop, and the potential market opportunity in RM/NVD/P/DR/DME. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success, costs, and timing of regulatory submissions and pre-clinical and clinical trials, including enrollment and data readouts; (ii) regulatory requirements or developments; (iii) changes to clinical trial designs and regulatory pathways; (iv) changes in capital resource requirements; (v) risks related to the inability of Ocuphire to obtain sufficient additional capital to continue to advance its product candidates and its preclinical programs; (vi) legislative, regulatory, political and economic developments, (vii) changes in market opportunities, (viii) the effects of COVID-19 on clinical programs and business operations, (ix) the success and timing of commercialization of any of Ocuphire’s product candidates, including the scalability of Ocuphire’s product candidates and (x) the maintenance of Ocuphire’s intellectual property rights. The foregoing review of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and may be filed by the Company from time to time with the SEC. All forward-looking statements contained in this presentation speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.    The Company makes no representation or warranty, express or implied, as to the accuracy or completeness of the information contained in or incorporated by reference into this presentation. Nothing contained in or incorporated by reference into this presentation is, or shall be relied upon as, a promise or representation by the Company as to the past or future.  The Company assumes no responsibility for the accuracy or completeness of any such information. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market shares and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates.  The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products.  
 

 Two Lead Assets for Front and Back of the Eye  Nyxol eye drops with > 650 patients treated across 12 trials (505(b)(2) pathway)  APX3330 oral tablets with > 340 patients treated across 11 trials (NCE pathway)  Four Large Markets with Unmet Needs in Reversal of Mydriasis (RM), Presbyopia, Night Vision Disturbance (NVD), and Diabetic Retinopathy  Differentiated and novel MOAs  Limited to no competition  Successful Execution of Trials with 6 Positive Phase 3 & Phase 2 Data Read-outs for Nyxol in RM, Presbyopia, and NVD  Potential 2023 commercialization opportunities in RM   Near-term initiation planned for Presbyopia VEGA Phase 3 program with Nyxol alone and Nyxol with 0.4% Low Dose Pilocarpine as adjunctive therapy  Track Record of Delivering on Timelines and Capital Efficiency  $17 million cash reported at 6-30-22 sufficient for operations through 3Q 2023  Low-cost, fast-enrolling, short-duration clinical trials  Favorable precedent regulatory environment for ophthalmic drug approval  Upcoming Catalysts in 2H22:  APX3330 ZETA-1 P2b trial for DR/DME 2H22  NDA Filing for Nyxol for RM LATE 2022  P= Presbyopia  RM = Reversal of Mydriasis   NVD = Night Vision Disturbances  DR/DME = Diabetic Retinopathy/Diabetic Macular Edema   3  Ocuphire PharmaNasdaq: OCUP 
 

 Ophthalmology is Ripe for Partnering   Prolific FDA Ophthalmology Division  Deal Activity  April 2021  Novartis / Alcon  $355 M  September 2021  REGENXBIO / Allergan  $1.75 B  October 2021  Théa / Curacle  ~$2 B  December 2021   Rayner / Omidria  ~$1 B  December 2021  Novartis / Gyroscope  ~$1.5B  January 2022  Théa / Akorn  Undisclosed  May 2022  Alcon / Kala  $385 M  New Product Approvals  Allergan – Vuity™   Oyster Point – Tyrvaya™  Bausch Health – Xipere™   Roche – Susvimo™  Novartis – Beovu™  Roche - Vabysmo™  Ocular Therapeutics – Dextenza™  Santen - Verkazia™  Samsung Bioepis - Byooviz™  Samsung Bioepis - Byooviz™ 
 

 Source: Eisai and Apexian Data; GlobalData Market Research Report, 2020; Company Estimates for US Market Size; *Ocuphire internal estimates  11  Completed  Phase 1 and Phase 2 Trials  >340Subjects Dosed  Patents to2034+  APX3330  Oral REF-1 Inhibitor  New Chemical Entity  Phase 2b Data 2H22   11  Completed  Phase 1,Phase 2, and Phase 3 Trials  >650Subjects Dosed  Exposure in Humans  28  Days  Patent Coverage2034+  Exposure in Humans  365  Days  Retina   Refractive   Two Late-Stage Clinical Assets Addressing Unmet Needs in Multiple Large Markets  Ocuphire Overview  Nyxol®   Novel α1/ α2 Blocker  505(b)(2)  NDA-Filing Ready  Presbyopia  Reversal of Mydriasis   Night Vision  Disturbances  Diabetic Retinopathy  Diabetic Macular Edema  Development Milestone  Prevalence (US)  Prevalence (US)  Development Milestone  Phase 2​  Enrolled  (103 subjects)  ~128 M  ~100 M  ~1 M  ~8 M  1st Phase 3  Positive Data  Phase 2  Positive Data  2 Phase 3  Positive Data  ~36 M 
 

 Indication  Product Candidate  Pre-clinical  Phase 1  Phase 2  Phase 3  Regulatory  Approval  Anticipated Milestones  Reversal of Mydriasis (RM)   Nyxol®  Eye Drop  Positive MIRA-3 Phase 3 data in Q1 2022 (n=368)   Positive MIRA-4 Pediatric data in 2Q 2022 (n=23)  File Nyxol NDA for RM in late 2022  Presbyopia (P)  Nyxol®  Eye Drop  Positive VEGA-1 Nyxol alone data in Q1 2022 (and in combination with LDP in mid-2021)   VEGA Phase 3 program planned to initiate in 2H 2022 for single agent and combination with LDP  Presbyopia (P)  Nyxol® +   0.4% Low Dose Pilocarpine (LDP)   Eye Drops  Dim Light or   Night Vision Disturbances (NVD)  Nyxol®  Eye Drop  Positive LYNX-1 Phase 3 data in 2Q 2022 (n=145)  Diabetic Retinopathy (DR)/ Macular Edema (DME)   APX3330   Oral Pill  ZETA-1 Phase 2b data expected in  2H 2022  (n=103)  DME or Wet Age-Related Macular Degeneration (wAMD)  APX2009 (Intravitreal or   Local Delivery)  Seeking partner funding for IND enabling studies and further development  Looking Ahead: Ocuphire Pipeline & Clinical Milestones  Note: 0.75% Nyxol (Phentolamine Ophthalmic Solution) is the same as 1% Nyxol (Phentolamine Mesylate Ophthalmic Solution)  Multiple Phase 3 & Phase 2 Clinical Data Readouts Anticipated this Year           Phase 2b Fully Enrolled             
 

 7  Reversal of Mydriasis  P  NVD  Presbyopia  Night Vision Disturbance  Nyxol®  Eye Drops  Three Indications  Nyxol as a Single Drop for Presbyopia  Nyxol with LDP Adjunctive Therapy  1  0.4%   2  RM 
 

 Nyxol’s Differentiated MOA as an Alpha-1 Blocker  No Engagement of Ciliary Muscle No Headaches and Lower Risk of Retinal Detachment  Phentolamine is the Active Ingredient in Nyxol: a Non-selective α1 & α2 Antagonist  505(b)(2) Regulatory Pathway Supported by Phentolamine Approval for 2 Indications:  Regitine® (Pheochromocytoma) – intravenous injection approved in 1952  OraVerse® (Reversal of oral anesthesia) – intramuscular injection approved in 2008  Nyxol blocks α1 receptors only found on the Iris Dilator Muscle  ↓  Decreases Pupil Size   (Moderate Miosis)  Without affecting the iris sphincter or ciliary muscles  Iris Dilator Muscle   Iris Sphincter and Ciliary Muscles  Company websites  Pilocarpine  Aceclidine  Carbachol  Phentolamine   (Nyxol)  Miotic Drugs  RM  P  NVD 
 

 Nyxol: 0.75% Phentolamine Ophthalmic Solution  Preservative Free, EDTA Free, and Stable  Efficacy Data   Favorable Safety Profile  Durable  Nyxol Improves Vision by Decreasing Pupil (~1-1.5mm)  ↑ Near Vision  ↑ Distance Vision  ↑ Contrast Sensitivity (night)  No Systemic Effects  No Changes in Blood Pressure  No Changes in Heart Rate  Well-Tolerated Topical Effects  Mild, Transient, Reversible Eye Redness  IOP Unchanged or Decreased  Minimal to No Headaches   Effects Last ≥ 24 Hours  Chronic daily dosing of Nyxol at bedtime reduces pupil size for up to 24 to 36 hours  Nyxol Product Candidate Profile  Nyxol Clinical Trials  Novel, Differentiated Alpha 1/2 Blocker Eye Drop for Refractive Indications  RM  P  NVD 
 

 10  RM  Nyxol®forReversal of Mydriasis (RM)  Mydriasis or dilated eyes causes:​  heightened sensitivity to light ​  inability to focus ​  reading, working, and driving difficulty​  halos and glare  headaches  I have to visit my retina MD for my monthly injections, where I am dilated. Being dilated every month is a huge burden on my day.                                    
 

 Summary of MIRA FDA Registration Trial Designs  Source: In order from left to rightMIRA-2 Registration Trial NCT# 04620213 MIRA-3 Registration Trial NCT# 05134974  MIRA-2  1st Phase 3  MIRA-3  2nd Phase 3  US Sites  12  16  Subjects Enrolled  185  368  Eligibility  Healthy ≥ 12 years old  Healthy ≥ 12 years old  Randomization  1:1  2:1  Mydriatic Agents  2.5% Phenylephrine, 0.5% Tropicamide and Paremyd  2.5% Phenylephrine, 0.5% Tropicamide and Paremyd  Positive Data Readout  1Q 2021  1Q 2022  Primary Endpoint  % of subjects (study eye) returning to baseline (within 0.2 mm) pupil diameter (PD) at 90 min​  Secondary Endpoints  % of subjects returning to baseline PD at 0min to 24h (overall, by mydriatic agent, by iris color)  Mean time to return to baseline PD  Mean change in pupil diameter at all timepoints   Distance-corrected near vision  Accommodation (Tropicamide/Paremyd)  Safety and tolerability  RM  Randomized, Double-Masked, Placebo-Controlled, Parallel, Multi-Center, One-Day Trials  Total Exposure To Nyxol  >330  >550  Total Subjects Enrolled 
 

 Primary Endpoint Achieved in Two FDA Registration Phase 3 Trials  Source: (Left panel) MIRA-3 Table 14.2.1.1 (mITT); (Right panel) MIRA-2 Table 14.2.1.1 (mITT). Data include all three mydriatics (Phenylephrine, Tropicamide, Paremyd).  Rapid, Consistent and Sustained Reversal of Pupil Dilation with Nyxol  MIRA-3 Phase 3 Trial  MIRA-2 Phase 3 Trial  RM  0 
 

 Planned NDA Package Incorporates Positive Data from MIRA Trials   Nyxol Significantly Reduced PD in Subjects Ages 3 & Over with Favorable Safety and Tolerability  MIRA Clinical Trials  RM  No deaths, serious AEs, or withdrawals due to AEs  All treatment related AEs were mild in severity  The only AE occurring in ≥ 5% of subjects treated with Nyxol was mild and transient conjunctival hyperemia and instillation site discomfort (11% Nyxol vs. 0% placebo)   No distance visual acuity loss  No change in vital signs  Completion of MIRA-4 study satisfies Pediatric Research Equity Act (PREA) requirement   Efficacy  Safety  Pivotal trials met primary endpoint of return to baseline PD at 90 minutes after dilation  MIRA-3 Phase 3 (58% Nyxol vs. 6% placebo, p<0.0001)  MIRA-2 Phase 3 (49% Nyxol vs 7% placebo; p<0.0001)  MIRA-4 pediatric (age 3-17) trial 64% Nyxol vs. 25% placebo  Met key endpoints with high statistical significance in MIRA-2 & MIRA-3  Efficacy across all 3 mydriatic agents – phenylephrine, tropicamide, and Paremyd®   Efficacy in both light and dark iris colors  Efficacy with 1 or 2 drops  Over 60% subjects returned to baseline accommodation at 2-3 hours  Accelerated return to normal distance-corrected near visual acuity 
 

 NDA Submission Targeted For Late 2022  Multiple Positive Clinical Trials To Support Broad Label  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  MIRA-2Phase 3  MIRA-1 Phase 2b  MIRA-3 Phase 3  RM NDA Filing  Late 2022  n=32 crossover  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  n=185  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  n=368  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  MIRA-4  Pediatric  n=23  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  Production of 3 registration batches ✓  Manufacturing 
 

 Commercial Strategy With Cash Pay Model   Source: GlobalData Market Research Survey  Simple, Value-Driven, Capital-Efficient and Accelerates Adoption  RM  Low Adoption Hurdles:  No reimbursement or payors/PBMs  No training, dilations are routine  No specialty/retail pharmacies  No competition  58%  physicians would start prescribing Nyxol within 1st year*  Sell   Directly  Office  Strategic and/or  Distribution Partners  20,000 Ophthalmologists  46,000 Optometrists   3,000 Retinal Specialists  Preservative-Free  Single Unit Vial (5-pack)  Physician   Sells to   Patient  
 

 ~$500M+  US RM Market Opportunity  Reversal of Mydriasis (RM) Market Opportunity  With No Commercially Available Treatment, Nyxol Could Achieve Significant Revenues   80 to 100 Average number of patients seen by an ECP per week   40 to 50 Average number patients dilated per week   20 to 25 Number of patients who choose reversal drop vials per week   1000 to 1,250 Total vials per year per ECP   10,000 to 16,000 Target number of ECPs   10 M to 20 M Total vials per year  Source: GlobalData Market Research SurveyCalculation: 100M Annual Eye Dilations X 65% X 80% X $10 per patient = $500+M Opportunity. Values Rounded, Not Exact.   ECP- Eyecare Practitioner   RM  Patient Willingness to Pay $10-$20+  80% of Patients Likely to Request Drop  65% Report Moderate to Severe Impact to Daily Function  MIRA Trials Represent 95% of Dilation Drops Used in Practice  100M Annual Eye Dilations  $100M to $200M   Potential Nyxol Revenue Opportunity 
 

 P  Nyxol® forPRESBYOPIA  17  Nyxol Alone  Nyxol with LDP Adjunctive Therapy  88% of patients expressed an interest in presbyopia-correcting drops across all ages and income groups  Source: Burke Healthcare Research April 2020, n = 1000 presbyopes ages 40-80 years old.  FDA approval of AbbVie Eye Drop a New Moment in Presbyopia                       10/29/21 
 

 Nyxol® and Nyxol + Low Dose Pilocarpine Presbyopia Eye Drops  Source: Nyxol® data from 12 completed trials; Pilocarpine product label and literature  Differentiated MOA with Two Potential Product Labels for Functional Near Vision Improvement  0.4%         0.75% Nyxol  0.4% LDP  Iris Dilator Muscle Inhibition  Iris Sphincter and Ciliary Muscles Activation  Evening drop  Phentolamine (alpha1/2 antagonist)  Novel MOA (iris dilator)   24+ hour PD durability  Moderate pupil reduction  Well-tolerated with no systemic effects  Stable, preservative-free, single-use vial  Pilocarpine (cholinergic agonist)  Known MOA on sphincter (and ciliary) muscle  Potent miotic at approved doses (1%, 2%, 4%)  Low concentration avoids known safety issues:  Headache, brow ache, and redness  Accommodative spasm causing loss of distance vision especially at night  Risk of retinal detachment  Daytime drop  Optimal Pupil Target is 2-3 mm  P  Two Drops Tunable Option  Nyxol with LDP as Adjunctive Therapy for Presbyopia  Single Durable Drop  Nyxol as a Single Agent for Presbyopia 
 

 Presbyopia VEGA-1 Phase 2 Trial  Clinical trial NCT#04675151. DCNVA = distance-corrected near visual acuity . BCDVA = best corrected distance visual acuity   Completed 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 hour  Secondary:  Primary endpoint for Nyxol alone vs placebo  % of subjects with ≥ 2 and ≥ 3 lines gained at time points from 30 min to 6 hours  % of subjects achieving 20/40 or better vision  No loss of distance vision   Pupil diameter at time points  Safety and tolerability (redness)  Endpoints  Visit 1  VEGA-1  Randomization  4 arms  0.75% Nyxol   Placebo  17 US sites  150 presbyopic patients  Visit 2   (Day 5)  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  (4 doses)  Males or females ≥ 40 and ≤ 64 years of age  DCNVA of 20/50 Snellen equivalent or worse in photopic conditions in each eye & binocularly  BCDVA of 20/20 Snellen equivalent or better in each eye under photopic conditions  No limitation on axial length or diopters for myopia patients  Eligibility Criteria  P  Phase 2 Enrollment Completed Feb to May 2021 – 150 Subjects Reported Topline Results in June 2021 and Jan 2022 
 

 VEGA-1: Planned P3 Efficacy Endpoint Met by Nyxol and Nyxol+LDP  VEGA-1 TLR Table 14.2.2.2.1; Table 14.2.2.2; Table 14.2.1.7; Table 14.2.1.2  Nyxol Single Drop and LDP Combination Provide Statistically Significant 3-line Near Vision Gain  Nyxol as a Single Drop for Presbyopia  Nyxol with LDP Adjunctive Therapy  1  0.4%   2  Nyxol+LDP is statistically superior to Nyxol alone and LDP alone  p<0.0001  p=0.03  p=0.008  P  DCNVA Letters Gained  79% of subjects achieved ≥10 letter improvement in DCNVA at 1 Hour (p=0.005 vs placebo) and a similar trend at other time points  53% of subjects achieved ≥ 10 letter improvement in DCNVA at 12 hours (p=0.005 vs placebo) and a similar trend at other time points 
 

 VEGA-1: Improvement in Functional Near Vision  Similar trend was seen at all timepoints for charts  Baseline Inclusion: Photopic DCNVA of 20/50 or worse  Source: VEGA-1 clinical trial  Nyxol and Nyxol with LDP Both Provide Durable Improvement in Functional Near Vision  Nyxol as a Single Drop  1  Nyxol with LDP Adjunctive Therapy  56% achieved 20/40 or better at 12 hours  84% achieved 20/40 or better at 1 hour  Improvement in Snellen Equivalent  P  0.4%   2  Improvement in Snellen Equivalent  Snellen Acuity (Binocular DCNVA) 
 

 No serious AEs, most AEs were mild  No headaches, no brow aches, and no blurry vision AEs were reported  No loss in distance vision under photopic and mesopic lighting  ~5% mild, transient redness  No change in IOP  Safety  Nyxol and Nyxol+LDP Pooled Safety Findings  Met planned P3 endpoint at 12 hours (29%; p=0.02)  Efficacy  Met primary endpoint at 1 hour (60%; p=0.004)  Durable near vision gain at 12 and 18 hours  Durability  Durable near vision gain through at least 6 hours  56%   (12 hours post-dose)  Functional Vision   (20/40 or better)  84%   (1-hour post-dose)  Sustained PD reduction at least 18 hours  Reduction in PD  Sustained PD reduction at least 6 hours  Ages 40-64  No myopia exclusions  Light and dark irides  Breadth of Patients Showed Efficacy  Ages 40-64  20/50 or worse DCNVA  Light and dark irides  Summary Of Positive VEGA-1 Phase 2 Results   PP Population, VEGA-1 Trial  *Trend toward statistical significance even in smaller Nyxol arm from time 0 to time 6 hours (n=30); larger sample size for all arms planned in Phase 3 program  Nyxol and Nyxol + LDP has Demonstrated Efficacy Response & Well Tolerated Safety Profile   P  Single Durable Drop  Nyxol as a Single Drop  Two Drops Tunable Option  Nyxol with LDP Adjunctive Therapy  0.4%   Well-Controlled, Multi-Center Phase 2 Trial Evaluating Nyxol & Nyxol+LDP   Efficacy  2  1 
 

 Phase 3  Phase 2  Phase 1  Orasis  CSF-1 (Low dose pilo)  Ocuphire  Nyxol + 0.4% pilo  Visus  Brimochol® (carbachol + brim)  Other Cholinergic   Agonists*  Cholinergic  Agonist* (pilocarpine)  Lenz  Aceclidine;  Aceclidine + brim  Eyenovia  MicroLine (2% pilo)  Novartis  EV-06 / Dioptin  Alpha Antagonist  & pilocarpine*  Ocuphire  Nyxol (0.75% phentolamine)  Alpha   Antagonist  Presbyopia Eye Drops Competitive Landscape  * act on sphincter and ciliary muscles in dose-dependent manner  Corporate Websites, Grzybowski, A, Markeviciute A, Zemaitiene R. A Review of Pharmacological Presbyopia Treatment. 2020  Pupil modulation (miotic) MOA  Combination drugs  Soften lens MOA (not a miotic)  Nyxol is potentially differentiated:  New MOA class (iris dilator muscle)  Favorable safety and tolerability (e.g.: no headaches, no risk of retinal detachment)  24-hour durability and rapid onset  Broad range of patients  Nyxol+LDP is the only option offering tunability for more efficacy  Nyxol Creates a New, Differentiated MOA Class; Nyxol+LDP Offers Tunability Option  P  NDA  Allergan   VUITYTM;   1.25% pilo  Lens Softening 
 

 Potential ‘Best in Class’ Presbyopia Drop(s)  Product Attributes*  1) Efficacy (> 3-Line Gain w/o loss of 1 line in DCNVA - Primary Endpoint Responders)*  2) Safety: Loss of Distance in Mesopic  3) Tolerability: Headaches and Conjunctival Hyperemia  4) Durability (% responders at the longest timepoint)  Placebo Adjusted Values for Vuity ™ were 15-23% in Gemini 1 & 2; Placebo Adjusted Nyxol was 16% and Nyxol+LDP was 33% (all stat significant)  Source: Nyxol Data: ASCRS (July 2021) Abstract# 76645 (Phase 2) and VEGA-1; Abstract 74336 (Phase 3). VUITY™ Data FDA Label and AAO 2021 Presentation.  Nyxol and Nyxol+LDP Combination Data Differentiate on Efficacy, Safety, and Durability  Nyxol’s Potential Differentiated Solution  Nyxol  Nyxol+LDP  29%   (vs placebo 12%) (12 hours)  61%  (vs placebo 14%) (30 min)  No Loss  No Loss  No Headaches  <5% mild redness  No Headaches  ~5% mild redness  37% at 18 hours  37% at 6 hours  VUITYTM  26-31%   (vs. placebo 8-11%)   (3 hours)  No Loss  >5% Headaches  >5% redness  18% at 6 hours  Caveats of cross-trial comparisons for VUITYTM and Nyxol/LDP. Differences include age, severity of near vision loss, lighting conditions, doses, timing, and # of patients  Ocuphire  P 
 

 Presbyopia is a Burgeoning Market Opportunity   Source: 1. Global Prevalence of Presbyopia, 2018, Fortune Business Insights Reading Glasses Forecast 2016-2027, Cataract & Refractive Surgery Today, 2021, NEI 2010 data.2. Vitale S. et. Al. JAMA Ophthalmology, 2008, Vision problems, US, Arch. Ophthal, 2014, Vision Monday.  3. NEI/NIH https://www.nei.nih.gov/sites/default/files/health-pdfs/Presbyopia.pdf Values in Figure Rounded  VuityTM Approval Sets the Stage for Market Development of a New Category by Large Pharma   $500 M+    Revenue Opportunity  Private Cash Pay  Vuity™ List Price $79  ~$8B+   Estimated US Presbyopia Market Opportunity  Pseudophakes  Cataract surgery for artificial lens  Hyperopes  Poor Near Vision  due to shorter eyeball  Myopes  Poor distance Vision/ elongated eyeball  Emmetropes  No refractive error/post-Lasik  9M  14M  30M  66M  Number of   Patients  Addressable   Market (25%)  US Market Opportunity  9M  2M  4M  8M  17M  2M  33M Patients  ~128M Presbyopes in the US  Low  < -6.0D  High  > -6.0D  ~$8 B+Market Revenues  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  26  NVD  Nyxol®   for  Dim Light or   Night Vision Disturbances 
 

 NVD LYNX-1 Phase 3 Registration Design  Note: Inclusion Criteria includes subjects with baseline mesopic LCVA of 20/63 or worse  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 diameter  Visual 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  19 US sites  140 - 160 patients with NVD  Phase 3 Initiated in Dec 2020; 145 Patients Enrolled  Top Line Results Reported May 19, 2022  Day 0  Day 8  Assessments  Primary Endpoint  Day 15  Assessments  NVD 
 

 LYNX-1: Nyxol Met Primary and Secondary Endpoints in NVD  Source: LYNX-1 clinical trial; PP population; mLCVA: mesopic low contrast visual acuity; pLCVA: photopic low contrast visual acuity  Significantly Higher % of Nyxol Treated Subjects Gained ≥15 Letter and ≥10 Letter From Baseline  NVD  Peripheral imperfections scatter light when pupils enlarge in dim light, causing halos/starbursts,/glare that impair vision  The imperfections may be caused by LASIK surgery, IOL implants, certain types of cataracts (cortical), and natural reasons (especially dry eye and age)   Symptoms cannot be properly corrected by any type of lens (reading glasses, contact lenses) or surgical procedures  The Problem  The Solution  47% (vs 24% placebo) of subjects achieved ≥ 10 letter improvement in mLCVA at Day 15 (p<0.05)*  No Treatment Options for NVD  n=73 n=70  n=73 n=68  30% (vs 7% placebo) of subjects achieved ≥ 10 letter improvement in pLCVA at Day 15 (p<0.05)* 
 

 Summary of Positive LYNX-1 Phase 3 Results For Nyxol Eye Drops  Source: mITT Population, LYNX-1Trial  Data Support a Favorable Benefit/Risk Profile For Subjects with NVD  No deaths or serious AEs  AEs occurring in >5% of Nyxol treated subjects included: instillation site irritation (9% vs 0% placebo), installation site pain (13% vs 0% placebo), dysgeusia (11% vs 0% placebo) and conjunctival hyperemia (9% vs 3% placebo)  84% of the AEs considered related to Nyxol were mild   No statistical difference in conjunctival hyperemia between treatment arms with evening dosing at Day 8 and Day 15  Efficacy  Safety  Met primary endpoint at Day 8 with 13% of subjects gaining 15 or more ETDRS letters of mesopic low contrast distance visual acuity vs. 3% on placebo (p<0.05)  Nyxol’s 3 line efficacy increased after 14 days of evening dosing, with 21% responders compared to 3% on placebo (p<0.01)  Nyxol statistically significantly reduced pupil diameter by a mean of ~1 mm on Day 8 and Day 15  Significant improvements in low contrast distance vision under photopic conditions were also observed  Nyxol demonstrated benefit in mesopic high contrast near vision   NVD 
 

 Market Opportunity in Dim Light or Night Vision Disturbances  GlobalData Market Research Report, 2020; Revenue potential based currently on Vuity Presbyopia pricing  No Currently Approved Treatments in Development with Ripe Opportunity for Growth   NVD  Post-IOL Implant  Post-Lasik  Cortical Cataracts  Night Myopia  2M  1M  26M  Number of Patients   Moderate to   Severe NVD  Addressable Market (60%)  US Market   Opportunity  0.3M  0.5M  11M  ~10 M Patients  US NVD Population ~38 M  9M  4M  No Approved Treatments  Pupil reduction with Nyxol may offer a potential solution to peripheral optical imperfections  ~$2 B+Market Revenues  7M  2M  0.3M  0.2M 
 

 31  Apx3330  ORAL tAblet  Diabetic   Retinopathy  and   Diabetic   Macular   Edema  DR  DME  I could lose my hearing, I could lose talking, but … it's frightening to lose my eyesight.   Patient Diagnosed with DR 
 

 Diabetic Retinopathy At a Glance  Larger Disease to Manage with Growing Diabetes  The number of people with DR expected to increase more than   14M by 2050  There are 8M adults in the U.S. with DR1  DR is the leading cause of blindness among working-age adults  If untreated, DR can rob people of their vision prematurely2,3  56% of patients   reported anxiety related to anti-VEGF treatment  DR/DME affects about 1 in 4 people with type 1 and type 2 diabetes  Majority of mild to moderate patients with DR are not treated with anti-VEGF due to injection fear and burden  DR  DME  Source:1. American Diabetes Association; International Diabetes Federation; Healthline;  2. Das UN. DME, retinopathy and age-related macular degeneration as inflammatory conditions. Arch Med Sci. 2016;12(5):1142-1157. doi:10.5114/aoms.2016.61918  3. Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000  $13B (2020)   Global Intravitreal Injection Revenues 
 

 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-α  Chemokines  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 Medicine  APX3330 is a small molecule oral drug candidate and a first-in-class inhibitor of Ref-1  APX3330 previously developed by Eisai for multiple hepatic inflammatory indications and later by Apexian for advanced solid tumors in 11 Phase 1 and 2 trials  Similar oncology origin as approved anti-VEGFs  MOA uniquely decreases both abnormal angiogenesis and inflammation by blocking pathways downstream of Ref-1  Extensively studied in over 20 in-vitro and animal studies with favorable efficacy and safety  DR  DME 
 

 Preclinical Data: Oral APX3330 Blocks Neovascularization  Source:  Silva et al. ARVO 2021 Annual Meeting; Li 2014;Pasha 2018;Jiang 2011 (Vldlr -/- : Very Low-Density Lipoprotein receptor knock-out mice)  Eisai PK clinical data APX_CLN_0002  Apexian preclinical data  Eisai preclinical data  Lesion Volume Decrease with Oral APX3330 in Murine Laser CNV Model Similar to EYLEA® Data  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   Vehicle  25 mg/kg  50 mg/kg  APX3330 Gavage OCT  Lesion Volume  APX3330  Efficacy was also seen after intraperitoneal and intravitreal injection APX33301  DR  DME  2 µg/ml in mouse plasma at 2hrs; 25 mg/kg oral single dose  ~20 µg/ml (120 mg/day) in human plasma   ~40 µg/ml (240 mg/day) in human plasma  Plasma concentration of APX33302  In addition, APX3330 detected in rat and mouse retina after oral dosing3,4  z  Linear PK Profile of APX3330  EYLEA L-CNV Mouse OCT Lesion Volume Data ~45%  MEAN±SEM  120 mg  240 mg 
 

 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)  ZETA-1 Clinical Trial is Sponsored by Ocuphire Pharma https://clinicaltrials.gov/ct2/show/NCT04692688?term=ZETA-1&draw=2&rank=1   Ongoing, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar To Eylea P3 DR Trial)  Primary: % of subjects with a ≥ 2 step improvement on the DRSS (Diabetic Retinopathy Severity Scale) score at week 24  Secondary:  Central subfield thickness (CST)  BCDVA (ETDRS)  DRSS change at week 12  Rescue subjects  Safety and tolerability  Exploratory:  Labs / PK  Endpoints  Phase 2b Enrolled 103 DR Patients from April 2021 to March 2022  Top Line Expected in 2H 2022  ZETA-1  Eligibility Screening  Randomization  APX3330 600mg/day (BID)  Placebo BID  25 US sites  90-100 participants with moderately severe-to-severe NPDR or mild PDR  Noncentral DME is permitted  1:1  Week 0  Week 12  Week 24  Week 4  Primary Endpoint  DR  DME 
 

 Why DRSS is an Important Endpoint?  Eylea® Panorama study  FDA Accepted Endpoint for EYLEA® in PANORAMA Pivotal DR Trial - 2 Step Improvement on the DRSS Score at Week 24     ETDRS Severity Level   Steps   Very Mild  Mild  Mod.  Sev.  VerySev.  Mild  Mod.  High Risk  Non-proliferative disease  Proliferative disease  PANORAMA: Reduction of DRSS Significantly reduces the incidence of Vision Threatening DR  Diabetic Retinopathy Severity Scale (DRSS)  Risk of vision-threatening events increases with worsening step progression  DR  DME 
 

 Masked Safety Findings from Ongoing ZETA-1 Trial  1. DME possibly study medication related (APX3330 or placebo)   2. Cellulitis (2 events in same subject), dyskinesia, transient ischemic event, COVID-19 and acute respiratory failure (same subject), progression of multivessel coronary artery disease, cholelithiasis, osteomyelitis, vertigo  3. Excludes 9 number of early withdrawals (4 due to AE, 3 due to lost to follow up, 2 due to withdrew consent.   Note: ZETA-1 Interim Data as of database 6/15/22 with complete monitoring before final database lock; assumes 50% subjects on APX3330   Favorable Safety Profile (as of 6/15/2022) Observed with 600 mg Oral Daily Doses in Diabetic Subjects  0   Major Organ Toxicities   (Liver, heart, kidney, brain, lung or vital sign abnormalities e.g., blood pressure or heart rate)  Oral APX3330 safety profile consistent with that seen in prior trials ​  >7000Subject-Days of   at 600mg/day  APX3330 Exposure   10 SAE  in 8/103 Subjects  0  Treatment Related  10   Unrelated2  70%Subjects completed thru Week 24  103   Subjects Enrolled  100%Subjects completed thru Week 12 3  4 subjects withdrew due to an AE  DME, dyspnea, osteomyelitis, syncope  145 TEAEs   In 60/103 Subjects (58%)  121  Unrelated  24  Treatment-Related  7 Moderate   0 Severe  Diarrhea, DME1, pruritis, urticaria, blurry vision, decrease in hemoglobin levels, decrease in hematocrit levels  74 Mild  37 Moderate  10 Severe  17 Mild   DR  DME 
 

 Novel MOA for treating retina   ↓ Inflammation   ↓ Abnormal Angiogenesis  Convenient Oral Dosing for Patient Compliance   Allow Daily vs. Episodic Exposure  Oral pill may reduce the burden of   frequent anti-VEGF injections  >9000 Subject-exposure days* at ≥600 mg/day dose  Few Systemic Adverse Effects  < 5% Mild Gastrointestinal (diarrhea)  < 5% Mild Skin Rash (reversible)  No Organ Toxicity (Liver, Cardiovascular {BP, HR}, Kidney, Neurologic, Pulmonary)  No Ocular Effects  No observed ocular AEs  APX3330 Product Candidate Profile for Multiple Retinal Indications  *11 completed Phase 1 and Phase 2 clinical trials by Eisai and Apexian; along with ongoing ZETA-1 trial by Ocuphire (*includes ~103 subject)  Oral, First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data  APX3330: Well-tolerated Oral Dose up to 600mg/day  Twice Daily Dosing  DR  DME  Expected Efficacy Data  Favorable Safety Profile 
 

 Diabetic Retinopathy  PDR (DRSS >60)  Moderate to Severe NPDR (DRSS 43-53)  Mild NPDR  34 Million Diabetics in US  10 M  6M  1M  1M  ~$8 M+DR Patients  DME  1M  Wet AMD  2M  Dry AMD  10M+  RVO  2M  GA  1M  DR  DME  Broad Opportunities to Treat Retinal Diseases with APX Platform   APX3330 May Treat Patients Across Retinal Diseases as Single Agent or Adjunctive Therapy  Anti-VEGF treatments  APX3330  APX2009 / APX2014 / APX3330 (Local Delivery)  US Market   Opportunity  Addressable Market  Potential First Oral Rx for Retina Diseases  APX3330  Inflammatory component is common across these retina indications and potentially addressable by the MOA of Ref-1   Source:1. American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions;  2. Das UN. DME, retinopathy and age-related macular degeneration as inflammatory conditions. Arch Med Sci. 2016;12(5):1142-1157. doi:10.5114/aoms.2016.61918  3. Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000  4. Estimates are provided by the National Eye Institute, FactSheet, Global Data, and Research and Markets. Estimated values are rounded. 5. Estimated prevalence in the U.S.  ~$10B+  Market Revenues 
 

 40  Milestones   Team/Boards   Financial Data 
 

 Track Record of Achieving Milestones  Exciting News Cadence  Ongoing Partnering Discussions with Leading Ophthalmic Companies (including Europe and Asia)  2021 – 1H 2022  2H 2022 – 2023  Submit Nyxol NDA for RM   Report Phase 2b Data for DR/DME (ZETA-1)  Initiate VEGA-2 & VEGA-3 Phase 3 Presbyopia Trials  Initiate LYRA-1 Long-term Safety Trial  Potential NDA Approval for RM  Establish Commercial Partnership  Report VEGA-2 Presbyopia Data  Multiple Positive Data Readouts in 2021-1H 2022 with Multiple Catalyst Ahead 
 

 Ocuphire Management Team  Decades of Biotech and Drug Development Experience  Mina Sooch, MBA  President & CEO   and Founder  Drey ColemanVP, Clinical Operations  Amy Rabourn, CPA  VP, Finance  Charlie Hoffmann, MBA  VP Corporate Development   and Operations  Mitch Brigell, PhD  Head, Clinical Development   and Strategy  Daniela Oniciu​, PhD  Global Head, R&D, Chemistry  and Product Development  Ronil Patel, MS  Senior Director BD and   Market Strategy  Chris Ernst  Global Head, QA  and Manufacturing  Barbara Withers, PhDVP, Clinical and Regulatory Strategy  Bindu Manne  Head, Market Development and Commercialization  Laura Gambino  Director, Project Management 
 

 Ocuphire Board of Directors   Sean Ainsworth, MBA  Lead Independent Director,   Board Director ​  James Manuso, PhD/MBA  Board Director​  Jay Pepose, MD, PhD  Board Director  Richard Rodgers, MBA  Board Director   Susan Benton, MBA  Board Director​  Cam Gallagher, MBA  Chair, Board Director  Mina Sooch, MBA  Vice-Chair, Board Director   President & CEO  Seasoned Directors with Decades of Drug Development, M&A/Financings, and Ophthalmology 
 

 Ocuphire's World-Class Medical Advisory Board  Fortunate for the Insights of Leading KOLs & Drug Candidate Co-Founders (Ant. Seg | Retina)  James Katz, MD  University of Illinois  Jay Pepose, MD, PhD  UCLA School of Medicine  Thomas Samuelson, MD  University of Minnesota   Paul Karpecki, OD  Indiana University  Eliot Lazar, MD  Georgetown University  Marguerite McDonald, MD  Columbia University  David Boyer, MD  Chicago Medical School   Mark Kelley, PhD  Indiana University  Co-Founder Apexian/APX3330  elCON Medical  Michael Allingham, MD, PhD  University of North Carolina  Peter Kaiser, MD  Harvard Medical School  Jeffrey Heier, MD  Boston University   Y. Ralph Chu, MD  Northwestern University  Douglas Devries, OD  University of Nevada  David Brown, MD  Baylor University  Mitch Jackson, MD  University of Chicago  David Lally, MD  Vanderbilt University  Refractive Specialist  Refractive Specialist  Refractive Specialist  Glaucoma Specialist  Refractive Specialist  Retinal Specialist  Retinal Specialist  Retinal Specialist  Retinal Specialist  Retinal Specialist  Refractive Specialist  Refractive Specialist  Retinal Specialist  Optometry   Optometry  
 

 OCUP – Market Snapshot   Source: FactSet  Active Trading Volume and Sufficient Cash Runway Through 3Q 2023   NASDAQ: OCUP  Price/share  $2.79  As of 8-11-22  Market Cap  $57 M  As of 8-11-22  Shares Outstanding  20.6 million  As of 10Q (6-30-22)  Cash  $17 M  As of 10Q (6-30-22)  Cash Runway  Sufficient through  3Q 2023  As of 10Q (6-30-22)  Average Daily Volume  ~120 K  60-day trailing average  Research Analyst   Coverage on OCUP  John Newman  Canaccord Genuity  Kristen Kluska  Cantor Fitzgerald  James Molloy  Alliance Global Partners  Sean Kim  Jones Trading  Matthew Caufield  H. C. Wainwright 
 

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