Form: 8-K

Current report filing

March 29, 2022


Exhibit 99.1

 MIRA-3 Phase 3 Trial Results Conference Call  March 29, 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, cash runway, and future clinical trials in reversal of mydriasis (RM), presbyopia, night vision disturbance (NVD) and diabetic retinopathy (DR)/diabetic macular edema (DME), and the potential market opportunity in RM. 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 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 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.  
 

 Agenda and Participants  Highlights and Overview  Topline MIRA-3 Phase 3 Clinical Trial Results for Nyxol in Reversal of Mydriasis (RM)  Reversal of Mydriasis Market Opportunity  Upcoming Milestones  Q&A  Participants  Mina Sooch, MBA, President and CEO  Jay Pepose, MD, PhD, Medical Advisory Board and Board Member  Mitch Brigell, PhD, Head of Clinical Development  Susan Benton, MBA, Corporate Board Member  Bindu Manne, Head of Market Development and Commercialization  Charlie Hoffmann, MBA, VP of Corporate Development and Operations  Amy Rabourn, MAcc, VP of Finance  Second Phase 3 RM Trial Topline Readout as Planned in 1Q22 
 

 Highlights and Overview 
 

 Key Takeaways from Nyxol’s MIRA-3 2nd Phase 3 RM Trial   MIRA-2 and MIRA-3 topline data.  MIRA-3  58% vs. 6% p<0.0001  MIRA-2  49% vs. 7% p<0.0001  Key Secondary Endpoints Met Statistical and Clinical Significance 
 

 Addressing Unmet Needs in Large Markets  Source: Eisai and Apexian Data; GlobalData Market Research Report, 2020; Company Estimates for US Market Size; *Ocuphire internal estimates.  Significant Preclinical & Clinical Data Supporting MOA, Efficacy and Safety  11  Completed  Phase 1 and Phase 2 Trials  >340Subjects Dosed  Patents to2034+  APX3330  Oral REF-1 Inhibitor  New Chemical Entity (NCE)  Nyxol®   Novel α1/ α2 Blocker  505(b)(2)   10  Completed  Phase 1,Phase 2, and Phase 3 Trials  >600Subjects Dosed  Exposure in Humans  28  Days  Patent Coverage2034+  Exposure in Humans  365  Days  Refractive   Retina  Presbyopia  Reversal of Mydriasis   Night Vision   Disturbances  Diabetic Retinopathy  Diabetic Macular Edema  DR  DME  RM  P  NVD  US Market Opportunity  $2B - $4B  $10B - $20B  ~$500 M  US Market Opportunity  $10+B  Oral Rx Revenues* 
 

 Indication  Product Candidate  Pre-clinical  Phase 1  Phase 2  Phase 3  Regulatory  Approval  Anticipated Milestones  Reversal of Mydriasis (RM)   Nyxol®  Eye Drop  Reported MIRA-3 Phase 3 data in Q1 2022 (n=368)  MIRA-4 Pediatric safety study data expected in 2Q 2022 (n=23)  Presbyopia (P)  Nyxol®  Eye Drop  VEGA Phase 3 program planned to initiate in mid-2022  Presbyopia (P)  Nyxol® +   Low-Dose (0.4%) Pilocarpine   Eye Drops  Dim Light or Night Vision Disturbances (NVD)  Nyxol®  Eye Drop  LYNX-1 Phase 3 data expected 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  ✓ MIRA-3   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   MIRA-2    VEGA-1      Recent Positive Trial Data  ★ Ongoing Trial     ★ ZETA-1  ★LYNX-1     ★ MIRA-4     
 

 Nyxol’s Differentiated MOA as an Alpha-1 Blocker  Phentolamine Mesylate Reformulated as a Proprietary Topical Eye Drop  NyxolTM  Phentolamine Mesylate is the Active Ingredient in Nyxol: a Non-selective α1 & α2 Antagonist  Blocking α1  Reduces Pupil Size  Blocking α1  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 α1 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 
 

 Nyxol®forReversal of Mydriasis (RM)  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 
 

 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 α1) innervation stimulates   the iris dilator muscles   2 Classes of Mydriatic Agents  Tropicamide   (anti-cholinergic)  Phenylephrine   (α1 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 
 

 MIRA-3 Topline Phase 3 Results  Randomized, Parallel Arm, Double-Masked, Placebo-Controlled Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) to Reverse Pharmacologically-Induced Mydriasis in Healthy Subjects 
 

 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 
 

 Demographics  Nyxol  n=244  Placebo  n=124  Total  n=368  Demographics  Age (years): Mean   (Range)  34   (12-80)  36   (12-80)  35   (12-80)  Sex: Male n (%)   Female n (%)  92 (37.7%)  152 (62.3%)  59 (47.6%)  65 (52.4%)  151 (41.0%)  217 (59.0%)  Race: White n (%)  African American n (%)  Asian n (%)  Other^ n (%)  ^includes American Indian or Alaska Native; Native Hawaiian or Other Pacific Islander  182 (74.6%)  38 (15.6%)  22 (9.0%)  0 (0%)  93 (75.0%)  21 (16.9%)  9 (7.3%)  1 (0.8%)  274 (74.5%)  59 (16.0%)  31 (8.4%)  7 (1.9%)  Light Iris Color: n (%)  113 (46.3%)  58 (46.8%)  171 (46.5%)  Dark Iris Color: n (%)  131 (53.7%)  66 (53.2%)  197 (53.5%)  Treatment and Placebo Arms Were Balanced in MIRA-3 Phase 3 Registration Trial  Source: MIRA-3 Table 14.1.2.1 (ARP) (mITT).  Notes: 32 pediatric subjects 12-17years old were enrolled in the trial.  Race is more than 100% given subjects could check more than one category.  Demographics represent all randomized population (ARP) of 368 which is the same as Safety Population and Modified-Intent-to-Treat (mITT).  Per Protocol (PP) Population is 345, excludes 23 subjects who did not dilate more than 0.2 mm 1 hour after receiving mydriatic drop.  RM 
 

 Baseline Characteristics Study Eye  Nyxol  n=248  Placebo  n=120  Total  n=368  Baseline Characteristic  Baseline Pupil Diameter Mean (mm)  5.1  4.9  5.1  Max Dilated Pupil Diameter Mean (mm)  7.2  7.1  7.2  Accommodation   Mean (diopters)   7.4  7.6  7.5  BCDVA letters  55 letters = 20/20  57  57  57  DCNVA letters  70 letters = 20/20   65  65  65  IOP (mmHg)  16.2   16.1  16.1  Treatment and Placebo Arms Were Balanced Across Ocular Measures in the MIRA-3 Trial     Source: MIRA-3 Table 14.1.2.1 (ARP) (mITT).  RM 
 

 Primary Endpoint: 58% of Subjects’ Study Eye Returned to Baseline at 90 Min  Source: MIRA-3 Table 14.2.1.1 (mITT). Data include all three mydriatics (Phenylephrine, Tropicamide, Paremyd).  Nyxol Statistically Better Than Placebo Starting At 1 Hour And All Subsequent Timepoints  MIRA-3 Phase 3 Trial  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 Trial  RM 
 

 Comparison of One Drop (Fellow Eye) with Two Drops (Study Eye)   Source: MIRA-3 Table 14.2.1.1 (mITT). Data includes all three mydriatics (Phenylephrine, Tropicamide, Paremyd).  Similar 52% of Subjects Return to Baseline at 90 Minutes with a Single Drop of Nyxol  RM  MIRA-3 Phase 3 Trial 
 

 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 
 

 Mean Pupil Diameter Over Time by Mydriatic Agents  Source: MIRA-3 Table 14.2.2.3. (mITT).  The p-values are change from max pupil dilation treatment compared to placebo. Standard Error bars are shown.   Nyxol Reduced PD With All Mydriatic Agents; More Rapidly with Phenylephrine as Expected  MIRA-3 Phase 3 Trial  Mean PD - Study Eye (mITT)  RM  p=0.001  Mydriatic  Max Dilation;   Treatment  1.5  1.5 
 

 Mean Pupil Diameter Over Time by Eye Color  Source MIRA-3 Table 14.2.2.5-(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 Reduced Pupil Diameter Rapidly in Both Light and Dark Irides  MIRA-3 Phase 3 Trial  Mean PD - Study Eye (mITT)  24  0.5  0.5  1.5  1.5  RM  Max dilation;  Treatment  Mydriatic  p=0.0007  p<0.0001 
 

 Mean Time to Return to Baseline PD  Source: MIRA-3 Table 14.2.3.2 (PP Population).  Saving of ~4 Hours in Return to Normal PD Overall and Across Mydriatic Agents     Overall  Irides  (study eye)  Mydriatic  Agent  (study eye)  n=230  n=115   n=230  n=115   n=66  n=137  n=26  n=46  n=23  n=47  n=59  n=122  n=56  n=108  RM  5.0 hrs   3.4 hrs  
 

 Maximum Pupil Dilation Results in Loss of Near Vision  MIRA-3 Table 14.3.6.1.1 (Safety Population) (mITT). DCNVA- Distance-Corrected Near Visual Acuity.  Nyxol Returns Near Vision to Baseline Levels Statistically Faster Compared to Placebo  RM  Baseline Near Vision  MIRA-3 Phase 3 Trial  1.5 
 

 Summary of Safety Findings   There were no deaths, serious AEs, or withdrawals due to AEs  48 of 244 (20%) Nyxol treated subjects reported 101 AEs  All treatment related AEs were mild in severity  The only AE occurring in ≥ 5% of subjects treated with Nyxol, was conjunctival hyperemia (11% Nyxol vs. 0% placebo)   Less than 1% of subjects reported instillation site discomfort, pain, or irritation  Conjunctival hyperemia was observed to be mild and transient  Visual acuity (distance and near) was not adversely affected by Nyxol  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  Source: MIRA-3 Table 14.3.1.1; MIRA-3 Table 14.3.1.2.2; MIRA-3 Table 14.3.3.2 (Safety Population).  Nyxol was Well Tolerated with a Favorable Safety Profile   RM 
 

 Summary of Positive MIRA-3 Phase 3 Results for Nyxol Eye Drops  Met primary endpoint at 90 minutes with 58% of subjects returning to pre-dilation pupil diameter vs. 6% of placebo treated subjects (p < 0.0001)  Saving of ~4 hours in time to return to normal pupil diameter  Met key secondary endpoints with high statistical significance  Efficacy seen at all timepoints from 60 minutes to 24 hours  Similar efficacy for one drop and two drops  Efficacy across all 3 mydriatic agents – phenylephrine, tropicamide, and Paremyd®    Efficacy in both light and dark iris colors  Accelerated return to normal distance-corrected near visual acuity  Favorable safety and tolerability profile  No serious AEs, no drop-outs from AEs  No systemic or ocular AEs were observed in ≥ 5% of subjects, except for 11% mild, transient conjunctival hyperemia  NDA planned for late 2022  MIRA-3 Topline Reports   Confirms Prior Phase 3 Study Showing Substantial Benefit in Accelerating Reversal of Mydriasis  RM 
 

 Plans to NDA for Nyxol in RM 
 

 MIRA Program Evaluating Nyxol for the Reversal of Mydriasis  Efficient Clinical Programs have Positioned Ocuphire to Target NDA Filing in Late 2022  MIRA-1  MIRA-2  MIRA-3  MIRA-4  RM  NDA Filing  Phase 2b  Phase 3  Phase 3  Pediatric Safety  NDA Submission  2019  n=32 crossover  n=185  n=368  n=23  2021  2022  2022   2022  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  Primary Endpoint Met ✓  Secondary Endpoints Met ✓  RM  Fully Enrolled   3-11 years old 
 

 NDA Submission Targeted in Late 2022  Potential Regulatory Approval in 2023  Enrolled 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  Ongoing  RM 
 

 Reversal of Mydriasis Market Opportunity 
 

 Reversal of Mydriasis Unmet Need & Landscape  Source  1. Optician (2012)-Mydriatic Drugs: Practical Considerations  2. Pilocarpine FDA Label (2017)   3. 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 issues1,2   Optomap® is offered by optometrists to avoid dilations for ~$50 cash-pay, however images may provide limited view of retina and disease pathology3  No Currently Available Treatments  100M   Annual Eye Dilations  Nyxol’s MOA Uniquely Suited As A Reversal Drop For Dilations  The Problem  RM 
 

 Bottom-Up Calculation of Annual Dilated Eye Exams  ~100 M Annual Dilated Eye Exams are Performed in the US  *IQVIA 2020 sales data; KOL Interview;  GlobalData market research; and AOA Excel and Jobson Medical Information  ‘Bottom-Up Calculation’ assumes 48 total work weeks in a year  Supply side validation assumed each unit (bottle) has ~10 mL fill volume and each patient gets 2-4 drops  Number of Providers (X)  Average Number of Weekly Exams (Y)  Estimated % Patients Dilated(Z)  Total(X*Y*Z) * 48 wk/yr  Optometrists  46,000  59  40%  ~52 M  Ophthalmologists  18,000  88  50%  ~38 M  Retina Specialists  3,000  150  50%  ~10 M  100M   Annual Dilated Eye Exams  Supply Side Validation: Based on the ~2 million total units of mydriatic agents sold in 2020, we calculated the total number of dilated eye exams to be ~125 million patients, consistent with demand side estimates.  Demand Side Validation  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 reversal drop  potential for Nyxol to be the only safe option  Cash pay (no reimbursement barriers) allowing for quicker adoption  Offering a significant value proposition to patients and practices  Shortened sales-cycle with acute use product   No training given dilations routine in practices  No specialty/retail pharmacy  direct to physician  “One product, several indications” offers efficiencies in commercial operations  RM 
 

 Pre-Commercial 2022 & Go-To-Market Strategy 2023  Sources: ASRS; AMA; AAO; Women in Optometry (WO); AOA Excel and Jobson Medical Information; Physician Interviews Conducted by Ocuphire; GlobalData market research  Activities Underway to Support Capital-Efficient Nyxol RM Commercial Launch  Physician  Targeting  Pre-Commercial Activity  Market   Development (KOLs)  Patient   Journey  Brand   Awareness  No approved drug/competition; data-mining for high volume practices  Landscape  No need for pharmacy; no reimbursement, private pay  Direct to Physicians  Dilations are a routine part of practice;   adoption requires no staff or patient training   Easy Adoption  Components of an Efficient Launch  Retina  3,000 Retinal Specialists  Ophthalmology  20,000 Ophthalmologists  Optometry  46,000 Optometrists   Potential Options for Commercialization  Go-To-Market Strategy  Work with strategic or channel partner with existing commercial ophthalmic products  Hire contract commercial organization  Build own salesforce  RM 
 

 Upcoming Milestones 
 

 Track Record of Achieving Milestones  Exciting 2022 News Cadence  Ongoing Partnering Discussions with Leading Ophthalmic Companies (including European and Asian Players)  2021  2022  Report Positive Nyxol Alone Phase 2 Data for Presbyopia  Report 2nd Phase 3 Data for RM (MIRA-3)   Report Phase 3 Data for NVD (LYNX-1)   Report Pediatric Data for RM (MIRA-4)   Submit Nyxol NDA for RM  Report Phase 2 Data for DR/DME (ZETA-1)  Initiate VEGA Phase 3 Presbyopia Program  Multiple Late-Stage Data Catalysts Expected in 2022 for Potential First NDA Approval in 2023