Full Press Release Details
Ocuphire Corporate Presentation May 19, 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 regulatory timelines, commercial timelines, product labels, cash runway, scalability, and
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
Differentiated, Late-Stage Pipeline for Front and Back of the Eye Nyxol with > 650 patients treated
across 12 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 trials Near-term Commercialization Opportunities in Multiple Large Unmet Markets Addressing 4 large markets with unmet needs: RM, Presbyopia, NVD, and DR/DME Successful trial execution with 6 positive Phase 3 & Phase 2 data
read-outs for Nyxol in RM, Presbyopia, and NVD Stable, small-molecule drugs with commercial scalability Robust and growing IP portfolio: US and global patents issued thru 2034 for both assets as well as new 2039 Nyxol patent issued for
presbyopia Multiple data readouts in 2022 with Track Record of Execution $19.2 million cash reported at 3-31-22 sufficient for operations into 2Q 2023 Highly experienced management, Board and KOLs with broad ophthalmic and biotech drug
development and commercialization success Low-cost, fast-enrolling, short-duration clinical trials Favorable precedent regulatory environment for ophthalmic drug approval Analyst coverage by Cantor, Canaccord, Jones Trading, Alliance
Global, and HCW Multiple Catalysts in 2022: Nyxol alone VEGA-1 P2 trial for P JAN 2022 Nyxol MIRA-3 P3 trial for RM MAR 2022 Nyxol MIRA-4 Pediatric trial for RM APR 2022 Nyxol LYNX-1 P3 trial for NVD MAY 2022 APX3330 ZETA-1 P2b trial
for DR/DME 2H22 NDA Filing for Nyxol for RM LATE 2022 Ocuphire Pharma Nasdaq: OCUP P= Presbyopia RM = Reversal of Mydriasis NVD = Night Vision Disturbances DR/DME = Diabetic Retinopathy/Diabetic Macular Edema 3
Ophthalmology - An Attractive Biotech Sector Favorable Regulatory Environment Source:1. Endpoint
Dec 29, 2021- Hitting a new record on drug approvals, the FDA offers a thumbs-up to another atopic dermatitis contender; 2. OIS Year in Review 2021; 3. Company press releases Demographics, M&A, Regulatory Approvals and Efficient Trials
Favor Ophthalmic Drugs New Product Approvals *sNDA 7 of 60 FDA Drug Approvals in 2021 Were Ophthalmic Drugs1 and 1 in 2022 Aging Population Ranibizumab biosimilar Active Partnering in 2021 April 2021 ~$2B October 2021 December
2021 ~$1.5B December 2021 $1.75B September 2021 Lower Cost, Quick Enrolling, Short Duration Clinical Trials Deal Activity December 2021 $670M $355M January 2022
Indication Product Candidate Pre-clinical Phase 1 Phase 2 Phase
3 Regulatory Approval Anticipated Milestones Reversal of Mydriasis (RM) Nyxol Eye Drop Reported positive MIRA-3 Phase 3 data in Q1 2022 (n=368) Reported positive MIRA-4 Pediatric data in 2Q 2022 (n=23) File Nyxol NDA for RM in
late 2022 Presbyopia (P) Nyxol Eye Drop Reported 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 mid-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 Reported 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 2H22 (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 Ongoing Trial
6 Reversal of Mydriasis P NVD Presbyopia Night
Vision Disturbance Nyxol Eye Drops 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 Phentolamine Mesylate Reformulated as a Proprietary
Topical Eye Drop Nyxol Phentolamine Mesylate is the Active Ingredient in Nyxol: a Non-selective 1 & 2 Antagonist Blocking 1 Reduces Pupil Size Blocking 1 Dilates Blood Vessels Phentolamine mesylate is approved for 2
indications: Regitine (Pheochromocytoma) - intravenous injection approved in 1952 OraVerse (Reversal of oral anesthesia) - intramuscular injection approved in 2008 505(b)(2) Regulatory Approval Pathway Nyxol blocks 1 receptors only
found on the Iris Dilator Muscle Decreases Pupil Size (Moderate Miosis) without Affecting the Ciliary Muscle Iris Dilator Muscle Iris Sphincter Muscle
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 Nyxol Product
Candidate Profile Nyxol Clinical Trials Novel, Differentiated Alpha 1/2 Blocker Eye Drop for Refractive Indications Favorable Safety Profile Efficacy Data Nyxol: 0.75% Phentolamine Ophthalmic Solution Preservative Free, EDTA Free, and
Stable Effects Last 24 Hours Chronic daily dosing of Nyxol at bedtime reduces pupil size for up to 24 to 36 hours Durable
9 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. I had a premium cataract procedure by my MD, and I was unable to see clearly for two days. My doctor said it was due to my dilation. I did not expect my
dilation to last that long. I have to stay indoors. They say it only lasts a few hours, but it lasts all day, and it is very annoying. RM Nyxol forReversal of Mydriasis (RM)
Problem: Dilated Eyes for Exams and Procedures Pharmacologically-induced pupil dilation is part of
standard care for annual and specialty eye exams but there is 6 to 24 hours of impaired vision including: Inability to Focus Photophobia (sensitivity to light) Cycloplegia (loss of accommodation) Difficulty Reading and
Driving Halos and Glare 1. GlobalData Market Research Survey; Oraverse and Regitine Label Patients Report Significant Side Effects after Dilated Eye Exam Note - Tropicamide and Cyclopentolate have same MOA NO REVERSAL DROPS COMMERCIALLY
AVAILABLE The Problem RM
Nyxol Has Potential To Be The Only Option For RM Physicians AVOID Use of Cholinergic Agonists
(Pilocarpine) Due to Safety Risk on Ciliary Muscle 1 Pilocarpine FDA Label (2017)2. Optician (2012)- Mydriatic Drugs: Practical Considerations 3. Lee DA, Higginbotham EJ, 2005. Glaucoma and its treatment: a review. Am J Health Syst Pharm
62, 691-699. Parasympathetic innervation stimulates the iris sphincter and ciliary muscle Sympathetic (primarily 1) innervation stimulates the iris dilator muscles 2 Classes of Mydriatic Agents Tropicamide
(anti-cholinergic) Phenylephrine ( 1 agonist) Reversal via the Ciliary Muscle by Cholinergic Agonists* is Not a Safe' Option Retinal tear has been reported in some patients, especially high myopes1 Induces accommodation spasm and
reduction in distance vision2 Induced anterior shift of the lens can increase the risk of acute angle-closure glaucoma2 High incidence of brow ache and headache following installation3 * Cholinergic Agonists include pilocarpine, carbachol,
and aceclidine. Note, pilocarpine is rarely used off-label for RM given these safety concerns. Nyxol is the only eye drop in clinical development for multiple indications with a MOA that does not affect the ciliary muscle RM
Reversal of Mydriasis Unmet Need & Landscape Source - Optos plc Pricing With No Commercially
Available Treatment, Nyxol is Uniquely Positioned as a New Reversal Drop At many annual eye exams and specialty visits, pupils are pharmacologically dilated, impairing vision for 6-24 hours Dilated eyes experience: Heightened sensitivity
to light Inability to focus, headaches Difficulty reading, working & driving Halos and glare Cycloplegia (loss of accommodation) Current Landscape: Rare off-label use of cholinergic agonists (e.g., pilocarpine) given ciliary
muscle safety issues Optomap is offered by optometrists to avoid dilations for ~$50 cash-pay, however images may provide limited view of retina and disease pathology No Currently Available Treatments 100M Annual Eye Dilations Nyxol's
MOA Uniquely Suited As A Reversal Drop For Dilations The Problem RM
MIRA-3 Phase 3 Registration Trial Design Randomized, Double-Masked, Placebo-Controlled, Parallel,
Multi-Center, One-Day Trial Mydriasis -1 Hour 1:1 Mydriatic Agent A, B, or C 0.75% Nyxol Placebo 16 US sites 368 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) pupil diameter (PD) at 90 min Key Secondary: % of subjects returning to baseline at 0min, 30min, 1h, 90 min 2h, 3h, 4h, 6h, 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 Endpoints MIRA-3 Started in Nov 2021 Enrolled 368 in Feb 2022 Phase 3 Results Reported March 2022 Screening Randomization 2 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 - A: 2.5% phenylephrine (alpha-1 agonist), B: 1% tropicamide (cholinergic blocker), C: Paremyd (combination) : Inclusion: Healthy 12 years of age Exclusion: Clinically
significant ocular trauma, surgery, or non-refractive laser treatment within the 6 months prior to screening; and recent or current evidence of ocular disease, infection or inflammation in either eye Key Eligibility Criteria RM
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
MIRA-3: Mean Pupil Diameter Over Time Source: MIRA-3 Table 14.2.2.1 (mITT). The p-values are change
from max pupil dilation treatment compared to placebo. Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd). Standard Error bars are shown. Nyxol Treatment Significantly Reduced PD Starting at 1 Hour Post-Dose Through
6 Hours MIRA-3 Phase 3 Trial 1.5 0.5 RM
Summary of MIRA Registration Trial Designs Source: In order from left to right MIRA-2 Trial NCT#
04620213 MIRA-3 Trial NCT# 05134974 Randomized, Double-Masked, Placebo-Controlled, Parallel, Multi-Center, One-Day Trials MIRA-2 Phase 3 MIRA-3 2nd Phase 3 Number of US Sites 12 16 Subjects Enrolled 185 368 Eligibility Healthy
12 years of age Healthy 12 years of age Randomization 1:1 2:1 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 % of subjects
(study eye) returning to baseline (within 0.2 mm) pupil diameter (PD) at 90 min >550 Total Exposure To Nyxol Total Subjects Enrolled >330 Over 300 subjects have been treated with Nyxol and evaluated at 24-hours in the MIRA trials
satisfying regulatory requirements for drug safety exposure for the acute RM indication In addition, 32 subjects were enrolled in positive MIRA-1 Phase 2 trial, a randomized, double-masked, placebo-controlled, crossover, multi-center trial
as well as MIRA-4 pediatric safety trial of 23 children. RM
Summary of Three Positive Late-Stage MIRA Clinical Trials Source: mITT Population, MIRA-2, MIRA-3 and
MIRA-4 Trial Confirms Phase 3 Trials with Favorable Safety and Tolerability Profile and Rapid Mydriasis Reversal 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 trial achieved 64% Nyxol vs. 25% Placebo (p<0.0001) Met key secondary endpoints with high statistical significance Efficacy across all 3 mydriatic agents - phenylephrine, tropicamide, and
Paremyd Efficacy in both light and dark iris colors Efficacy with 1 or 2 drops Accelerated return to normal distance-corrected near visual acuity Saving of ~4 hours in time to return to normal pupil diameter RM
NDA Submission Targeted in Late 2022 Potential Regulatory Approval in 2023 Completed trial with 23
subjects ages 3 to 11 per agreed FDA initial pediatric study plan Pediatric Safety Completed 2nd Phase 3 trial in RM (enrolled 368 subjects), which also meets 24-hour safety population exposure requirement P3 Clinical Trial Completed 3
registration batches; 1-year CMC stability will be available for NDA Manufacturing Submit NDA by late 2022, with expected approval review of 10 months 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. Preservative-Free Single Unit Vial (5-pack) Ongoing RM
~$500+M Estimated US RM Market Opportunity Reversal of Mydriasis (RM) Market Opportunity With
No Commercially Available Treatment, Nyxol May Achieve Significant Revenue Potential Patient Willingness to Pay $10 - $20+ 65% Report Moderate to Severe Impact to Daily Function 100M Annual Eye Dilations 80% of Patients Likely to Request
Drop 58% physicians would start prescribing Nyxol within 1st year 81% patients would be more likely to schedule yearly eye exams with a reversal drop 0 Current Commercially Available Treatments MIRA Trials Represent 95% of Dilation
Drops Used in Practice Source: GlobalData Market Research SurveyCalculation: 100M Annual Eye Dilations X 65% X 80% X $10 per patient = $500+M Opportunity 68% physicians would be willing to use Nyxol even if patients had to still wear
sunglasses within 1st hour GlobalData Market Research Findings RM
More Efficient Launch Opportunity for Nyxol in RM Launch is Poised to be Disruptive, Cost-Effective
and Not Payor-Driven Traditional Ophthalmic Launch Traditional Ophthalmic Launch Highly competitive markets (e.g., dry eye, glaucoma, allergy); little differentiation Launch success takes time given payor (reimbursement)
dependence Significant prior authorization & step-edits hurdles with burden to the practices Lengthy sales cycles and touchpoints due to chronic use and market access upkeep Significant product education requirement Complex
distribution channel including specialty and retail pharmacies "One product, one indication" commercial model is inefficient with fixed cost infrastructure Ocuphire's Nyxol RM Launch Ocuphire's Nyxol RM Launch No competition or approved