Form: 8-K

Current report filing

January 25, 2023


Exhibit 99.1

 ZETA-1 APX3330 Topline Results Investor Webcast  January 25, 2023 
 

 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 future clinical trials for APX3330, timing and occurrence of an end of phase 2 meeting with the FDA, the potential of a Phase 3 registration path for APX3330,  the success and timing of planned regulatory filings, business strategy, cash runway, scalability, the potential for APX3330 to be the first line of therapy for DR patients, and the potential market opportunity for the slowing of DR progression. 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) Nyxol partnership may not facilitate the commercialization or market acceptance of Ocuphire’s product candidates; (x) the success and timing of commercialization of any of Ocuphire’s product candidates, including the scalability of Ocuphire’s product candidates and (xi) 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 Speakers  Topic  ZETA-1 Key Takeaways and APX3330 Oral MOA  ZETA-1 Trial Design and Demographics   ZETA-1 Efficacy Findings   ZETA-1 Safety Findings   Overall Summary and Next Steps   Q&A  Mina Sooch, MBA  Founder and Chief Executive Officer  Mitch Brigell, PhD  Head of Clinical Development and Strategy  Charles Wykoff, MD, PhD  Vitreoretinal Specialist  Mark Kelley, PhD  APX Scientific Founder and Medical Advisor 
 

 ZETA-1 Key Takeaways and APX3330 Oral MOA 
 

 ZETA-1 Trial: Key Takeaways   APX3330 achieved statistical significance on a key pre-specified secondary endpoint of preventing clinically meaningful progression of diabetic retinopathy (as defined by binocular 3 or more steps worsening on the DRSS1) after 24 weeks of treatment   Trend toward more efficacy at 24 weeks vs 12 weeks, suggests that the 52-week Phase 3 trial may generate a larger signal due to an increase in % of placebo subjects who progress  Prevention of 3-step worsening (binocular) is a suitable endpoint for an oral, systemically drug  Ocuphire plans to go forward with this potential registration endpoint in Phase 3 following confirmation with the FDA in EOP2 meeting  Oral APX3330 demonstrated favorable safety and tolerability  Retinal KOLs feedback suggest that slowing of DR progression with an oral agent would be a useful treatment in patients with background DR and good visual function  If approved, APX3330 could be an important new primary preventative therapeutic option that could be used in a large number of diabetic patients who are earlier in their disease    diabetic retinopathy severity scoreSource: ZETA-1 Clinical Trial                
 

 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 and Ocuphire’s Scientific Advisor for APX program  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 
 

 ZETA-1 Trial Design and Demographics 
 

 DR/DME ZETA-1 Phase 2 Design  NPDR = non-proliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy ZETA-1 Clinical Trial is Sponsored by Ocuphire Pharma  Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar To Eylea P3 DR Trial)  Primary: % subjects with ≥ 2 step improvement on DRSS (Diabetic Retinopathy Severity Scale) at wk 24  Secondary:  DRSS worsening*  DRSS improvement*  Progression to vision threatening complications  Central subfield thickness (CST)  Best Corrected Distance Visual Acuity (BCDVA)   Rescue subjects  DME fellow eye status  Safety and tolerability  Exploratory:  Labs / PK  *Potential Phase 3 approvable endpoints  Endpoints  103 Subjects Enrolled (FPFV Apr 2021- LPLV Aug 2022)  Top Line Announced in Early 2023  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 in study eye and central DME allowed in fellow eye  1:1  Week 0  Week 12  Week 24  Week 4  Primary Endpoint  NPDR = non-proliferative diabetic retinopathy  PDR = proliferative diabetic retinopathy 
 

 Source: ZETA-1 Clinical trial  Key Eligibility Criteria in ZETA-1  Oral Medication Provides Binocular Treatment; DME Allowed in Fellow Eye  Inclusion  Exclusion  Males or non-pregnant females ≥ 18 years of age  At least one eye with DR DRSS 47, 53, or 61, confirmed by a central reading center) in which PRP and intravitreal injections of an anti-VEGF agent can be safely deferred for ≥ 6 months in the opinion of the Investigator   BCVA assessed by ETDRS protocol letters score of ≥ 60 letters (Snellen equivalent 20/63 or better) in the study eye  Body mass index (BMI) between 18 and 40 kg/m2, inclusive  Retinopathy from causes other than diabetes in study eye  Presence of center involved diabetic macular edema (DME) defined as a central subfield thickness (CST) ≥ 320 μm on SD-OCT   Center involved DME in the fellow eye is allowed  Prior treatment in study eye with focal/grid laser photocoagulation within the past year, PRP at any time, systemic or intravitrealanti-VEGF agents within last 6 months in study eye  Intraocular steroids including triamcinolone and dexamethasone implant within the last 6 months  Fluocinolone implant within the last 3 years  HbA1c ≥ 12.0%  Clinically significant systemic disease (e.g., uncontrolled diabetes, myasthenia gravis, cancer, hepatic, renal, endocrine, or cardio-vascular disorders) that might interfere as deemed by Investigator 
 

 ZETA-1: Demographics  ​  APX3330  n=51  Placebo​  n=52  Total​  n=​103  Demographics​  ​  ​  ​  Age (years): Mean ​  (Range)​  54.3   (26-81)​  58.3   (24-78)​  56.3   (24-81)​  Sex: Male n (%)​  Female n (%)​  24 (47%)​  27 (53%)​  26 (50%)​  26 (50%)​  50 (49%)​  53 (52%)​  Race: White n (%)​  African American n (%)​  Asian n (%)​  Other n (%)​  Ethnicity: Hispanic or Latino n (%)  Not Hispanic or Latino n (%)​  40 (78%)​  5 (10%)​  3 (6%)​   3 (6%)  28 (55%​)  23 (45%)  41 (79%)​  6 (12%)​  1 (2%)​  0 (0%)​  23 (44%)  29 (56%)  81 (79%)​  11 (11%)​  4 (4%)​  3 (3%)​  51 (50%)   52 (51%)  Time (Years) Since Onset of Diabetes:Mean  15  16  16  Well-Balanced Across Arms  Source: ZETA-1 Clinical Trial  
 

 ZETA-1: Baseline DRSS Scores Study and Fellow Eye   ​  APX3330  n=51  Placebo​  n=52  Total​  n=​103  DRSS Score – Study Eye​  ​  ​  ​  DRSS Category (Screening) Study Eye [n (%)]​  47 (Moderately severe to severe NPDR)​  22 (43%)​  18 (35%)​  40 (39%)​  53 (Moderately severe to severe NPDR)  25 (49%)​  28 (54%)​  53 (52%)​  61 (Mild proliferative diabetic retinopathy)  4 (8%)​  6 (12%)​  10 (10%)​  Well-Balanced Across Arms  Source: ZETA-1 Clinical Trial  ​  APX3330  n=45  Placebo​  n=49  Total​  n=​94  DRSS Score – Fellow Eye  ​  ​  ​  DRSS Category (Screening) Fellow Eye [n (%)]​  43 or Lower (Mild to moderate NDPR or better)  14 (31%)  12 (24%)  26 (28%)  47 (Moderately severe to severe NPDR)​  13 (29%)​  19 (39%)​  32 (34%)​  53 (Moderately severe to severe NPDR)  12 (27%)​  9 (19%)​  21 (22%)​  61 (Mild proliferative diabetic retinopathy)  1 (2%)​  4 (8%)​  5 (5%)​  65 or Higher (Moderate to severe prolif. DR)  5 (11%)  5 (10%)  10 (11%) 
 

 ZETA-1: Baseline Characteristics Study and Fellow Eye  APX3330  n=51  Placebo  n=52  Total  n=103  Baseline Characteristic  BCVA letters in Study Eye Letters Read (mean)  81  78  80   (20/25 Snellen)  BCVA letters in Fellow Eye Letters Read (mean)  76  77  77   (20/32 Snellen)  OCT Central Subfield Thickness in Study Eye (µm)  270  271  271  OCT Central Subfield Thickness in Fellow Eye (µm)  292  286  289  Intraocular Pressure in Study Eye (mmHg)  15  16  15  Systolic Blood Pressure (mmHg)  (mean)  136  139  138  Diastolic Blood Pressure (mmHg)  (mean)  82  80  81  Heart Rate (beats/min)  (mean)  78  76  77  Hemoglobin A1C (%)(mean)  8.4  8.3  8.3  Body Mass Index (kg/m^2)(mean)  31  31  31  Source: ZETA-1 Clinical Trial  Well-Balanced Across Arms  Good Visual Acuity  Fluid Below DME Definition of 320 micron (µm)  Note: Blood markers are normal range as baselines 
 

 ZETA-1 Efficacy Findings 
 

 10  81-85  71-75  Background on DRSS Assessment & Binocular DRSS  Diabetic Retinopathy Severity Scale (DRSS)  The ETDRS diabetic retinopathy severity scale (DRSS) is a categorical tool for clinical trials that contains 10 discreet steps from no retinopathy to severe proliferative retinopathy derived from the grading of fundus photographs for each eye at a central reading center. Each patients’ study eye had a baseline DRSS step of 5, 6 or 7 to be included in this trial.  Monocular calculation: Change in DRSS Step in a Single Eye (Study Eye or Fellow Eye)  Binocular calculation: Composite Change in DRSS Step in Study Eye and Change in DRSS Step in Fellow Eye  1  2  3  4  5  6  7  8  9  10  Step  DRSS 
 

 Percent of Subjects With ≥ 2-Step Improvement in DRSS From Baseline  Source: ZETA-1 Clinical Trial   Note: Large “N” indicates total number of participants within each arm for the mITT population. Small “n” indicates total number of evaluable eyes for each respective endpoint and arm.   Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting   ZETA-1 Did Not Meet the Week 24 Phase 2 Primary Endpoint (based on Anti-VEGF Precedence for DR)  n=46  n=47  n=39  n=40  n=14  n=24  n=11  n=22  Percent of Subjects With ≥ 2-step Improvement in DRSS From Baseline by Visit   (mITT) – Study Eye   Percent of Subjects With ≥ 2-step Improvement in DRSS From Baseline by Visit   (mITT) – Qualified Fellow Eye  
 

 In retina, opportunity for approval to show improvement OR worsening (prevention of progression)*  Precedent approvable endpoint for locally delivered drugs (non-systemic) in DR:  ≥ 2-step DRSS improvement in study eye  Eylea (Panorama trial)  Lucentis (Rise/Ride trials)  Oral/systemic drugs are different than anti-VEFG IVT as they treat both eyes  Therefore, a suitable evaluation is change in both eyes (binocular)  Potential approvable endpoints for systemic drug in DR (to be confirmed at the EOP2 FDA meeting) include:  ≥ 3-step binocular DRSS improvement   ≥ 3-step binocular DRSS worsening   ZETA-1 Phase 2 trial for APX3330 evaluated key secondary endpoints ≥ 3-step binocular DRSS improvement and worsening to inform design of the Phase 3 registration trial  Clinically Meaningful Registration Endpoints in DR  Source: ZETA-1 Clinical trial  Path Forward to Phase 3: Systemic Drugs Should Evaluate DRSS Change in Both Eyes  *Nair P, Aiello LP, Gardner TW, Jampol LM, Ferris FL III. Report From the NEI/FDA Diabetic Retinopathy Clinical Trial Design and Endpoints Workshop. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5127-5142. doi: 10.1167/iovs.16-20356. PMID: 27699406; PMCID: PMC6016432. 
 

 Source: ZETA-1 Clinical Trial   Note: Large “N” indicates total number of participants within each arm for the mITT-LOCF population. Small “n” indicates total number of evaluable eyes for each respective endpoint and arm.   Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting   Potential Phase 3 Endpoints as an Oral Drug; Results Improve with Time  Percent of Subjects With Improv. or Worsening in Binocular DRSS of ≥ 3-Steps   n=49  n=49  n=45  n=45  p=0.04  p=0.38  n=49  n=49  n=45  n=45  p=0.07  p=0.61  Percent of Subjects With Improvement or Worsening in DRSS of ≥ 3 Steps From Baseline   Binocular Eyes   (mITT-LOCF) - Week 12  Percent of Subjects With Improvement or Worsening in DRSS of ≥ 3 Steps From Baseline  Binocular Eyes  (mITT-LOCF) - Week 24 
 

 Percent of Subjects With Binocular Worsening in DRSS of ≥ 3-Step   Selected Primary Registration Endpoint for Phase 3, To Be Formally Confirmed at EOP2 FDA Meeting  p=0.04  p=0.07  Percent of Subjects With Worsening in DRSS of ≥3 Steps From Baseline by Visit   Binocular Eyes   (mITT-LOCF)   n=49  n=45  n=49  n=45     Source: ZETA-1 Clinical Trial   Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting   Note: Large “N” indicates total number of participants within each arm for the mITT-LOCF population. Small “n” indicates total number of evaluable eyes for each respective endpoint and arm.  Based on extrapolation from ZETA-1, ~25% of patients may progress by ≥ 3 steps in binocular DRSS over 1 year if untreated 
 

 Waterfall by Subject Binocular Change in DRSS at Week 24  Source: ZETA-1 Clinical Trial   Note: Images from Central Reading Center will be reviewed prior to EOP2 FDA meeting   8 Subjects in Placebo and 0 in APX3330 had a 3-Step DRSS Worsening at Week 24   ≥ 3 Steps  Worsening n=8   ≥ 3 Steps Worsening  n=0   Waterfall plots show subjects with worsening 
 

 Historic Data for Diabetic Patients on DR Progression  Source - Frequency of Evidence-Based Screening for Retinopathy in Type 1 Diabetes. N Engl J Med. 2017 Apr 20;376(16):1507-1516. doi: 10.1056/NEJMoa1612836. PMID: 28423305; PMCID: PMC5557280  The Worse the DRSS, the Higher the Risk of Vision Threatening Complications  Probability of developing PDR or DME is greater with higher baseline NPDR severity  Lucentis data shows that 28% untreated eyes will   worsen DRSS by ≥ 2-steps over 1 year  Source – Sun JK, Evidence for Diabetic Retinopathy Progression and Regression from Clinical Trials. Presented at NDI/FDA DR Clinical Trials Design and Endpoints Workshop, June 26, 2015.  DRSS Change from Month 36 to Month 48  Patients, %  Received Re-treatment During OLE (n=285)  No Re-treatment During OLE (n=82)  Stability of DR from Month 36 to month 48  Severe nonproliferative diabetic retinopathy (state 4)  Moderate nonproliferative diabetic retinopathy (state 3)  Mild nonproliferative diabetic retinopathy (state 2)  No retinopathy (state 1)  Cumulative Incidence, % 
 

 ZETA-1 Safety Findings 
 

 PK/Safety Data Findings  APX3330 PK/serum levels as predicted at 600 mg/day  Serum levels of APX3330 are consistent with previous findings in hepatitis and oncology trials  Fewer subjects lost 5 or more letters at week 24 with APX3330 compared to placebo  Limited treatment related AEs (mostly mild and transient)  Only rash (6% APX3330 vs 2% placebo) and pruritus (12% APX3330 vs 2% placebo) were seen more frequently in APX3330 than placebo  No treatment related serious TEAES   No effect on vital signs (BP, HR)  No effect on physical exam  No change in liver, kidney, or heart functions  No effect on IOP  No effect on clinical labs  ZETA-1 Clinical Trial (Safety Population)  Favorable Safety Data for Oral APX3330 
 

 Treatment Emergent Adverse Events  APX3330 Safety Similar To or Better Than Placebo  0  Treatment-Related AEs   involving liver, heart, kidney, brain, lung,   or vital signs   Oral APX3330 safety profile consistent with that seen in prior trials​  14 SAEs (in 11 Subjects)  3 unrelated  SAEs in APX3330  11  unrelated  SAEs in Placebo  211 Treatment Emergent AEs (64 Subjects)   91 (29 Subjects) APX3330, 120 (35 Subjects) Placebo  31  Treatment-Related AEs (in 21 Subjects)  APX3330  14 AEs in 10 subjects  (10 mild, 4 moderate, 0 severe)  4  withdrew   due to an AE  2 APX, 2 PBO  3  withdrew   consent or site closure  2 APX, 1 PBO  5  lost to  follow-up  2 APX, 3 PBO  ZETA-1 Clinical Trial Safety Population (subject to final review)  Placebo  17 AEs in 11 subjects   (8 mild, 9 moderate, 0 severe)  103   Subjects Enrolled  91Subjects completed thru week 24 
 

 Summary and Next Steps 
 

 APX3330 Product Candidate Profile for Multiple Retinal Indications  Source: ZETA-1 Clinical Trial; *1 subject had vision blur thought to be related by investigator in ZETA-1  Oral, First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data from 12 Completed Trials  Novel MOA for Treating Retina    ↓ Inflammation    ↓ Abnormal Angiogenesis   Daily vs. episodic exposure  Good Patient Compliance in ZETA-1 with Convenient Oral Dosing  APX3330 Demonstrated Slowing of Progression of Diabetic Retinopathy  Over 350 Subjects (Healthy, Liver, Cancer, Diabetic) Treated    Notably, Several Subjects Dosed ~1 Yr and Others 24-Wks  Few Systemic AEs Across All Doses (120mg-720mg)   < 5% Mild Skin Rash (reversible)   < 5% Mild Diarrhea  No Treatment-Related Organ Toxicity   (Liver, Cardiovascular {BP, HR}, Kidney, Neurologic, Pulmonary)  Minimal Ocular Side Effects*  APX3330: Well-tolerated Oral Dose up to 600 mg/day | Twice Daily Dosing  MOA and Efficacy Signals in DR  Favorable Safety Profile 
 

 Diabetic Retinopathy  PDR(DRSS >60)  Moderate to Severe NPDR (DRSS 43-53)  Mild NPDR  34 Million Diabetics in US  10M  6M  1M  1M  ~8M+DR Patients  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 with Multi-Billion Revenue Opportunity  APX3330  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.; DME- Diabetic Macular Edema; Age-related Macular Degeneration; Geographic Atrophy; Retinal Vein Occlusion  ~$10B+  Market Revenues  DME  1M  Wet AMD  2M  Dry AMD  10M+  GA  1M  Inflammatory component is common across these retina indications as well & potentially addressable by MOA of Ref-1  
 

 Landscape of Systemic Therapies for Diabetic Retinopathy  Ocuphire’s APX3330 is the Most Advanced Oral Drug Moving into EOP2 Mtg and Phase 3  www.clinicaltrials.gov  Company  Drug  Target/MOA  Indication  Route of Administration  Phase 1  Phase 2  Phase 3  Primary Endpoint/ Secondary Endpoints  LY333531  Protein Kinase C inhibitor  DR  Oral  ✓  ✓  ✕  2006  2002: BCVA 3-line  çAKB-9778  Tie2  DR  Subcutaneous  ✓  ✕  2019  2017: 2-step DRSS @wk24  APX3330  Ref-1 inhibitor  (Anti-VEGF and Anti-inflammatory)  DR  Oral  ✓  ✓  2020: 2-step DRSS @wk24  BAY1101042  Guanylate Cyclase activator  DR  Oral  ✓  ◌  2021: 2-step DRSS @wk24  AKST4290   CCR3 Eotaxin inhibitor  DR  Oral  ✓  ✕  2022  2021: 2-step DRSS @wk24  RG7774  CB2 receptor  (cannabinoid)  DR  Oral  ✓  ◌  2020: 2-step DRSS @wk36  BI 1467335  AOC3  DR  Oral  ✓  ✕  2021  2017: Primary:safety@wk12  Secondary: 2-step DRSS@wk12  OPL-0401  ROCK 1/2 inhibitor  DR  Oral  ✓  ◌  2021: 2-step DRSS @wk24  ✓   Completed  ◌   Ongoing  ✕   Discontinued  Note Two Tyrosine Kinase and a Plasma Kallikrein Inhibitors failed as orals in Phase 2 due to dose limiting adverse events (e.g., liver and cardiovascular) 
 

 APX3330 has Potential to be Early Preventative Therapy for DR Patients  Eylea® label; APX3330 Investigator Brochure, ZETA-1 clinical trial  Clinically meaningful decrease in diabetic retinopathy severity  OR  Early intervention with oral may prevent progression of DR to vision loss  Efficacy Signal  Intravitreal: Percent of patients with ≥ 2 step improvement on the DRSS score at week 24 and 52 compared to placebo in 2 well-controlled trials  Systemic: Percent of patients with ≥ 3-step worsening on binocular DRSS at week 24 and 52 compared to placebo in 2 well-controlled trials  Efficacy Signal  FDA  Physician/Patients  Safety  Non-Invasive Treatment Option  Safety  Approval depends on a product's benefit outweighing its risks in the intended population, this benefit should be evaluated in multi-center, 2-year clinical trials   FDA does not require comparative arm of approved anti-VEGF injections (Eylea) for DR  Non-Invasive Treatment Option  No major organ toxicities  Well-tolerated (e.g., AEs acceptable if mild and infrequent for oral)  Eylea®, although approved, is currently not used as standard of care because of the treatment burden for asymptomatic DR patients   Ability to be prescribed by wide-range of healthcare providers (ophthalmologists, optometrists, endocrinologists, primary care, etc.)  Oral option increases global access, especially in underserved regions 
 

 Key Takeaways and Next Steps   APX3330 is the most advanced oral program in development for diabetic eye disease  APX3330 demonstrated favorable safety with compelling potential to slow progression of diabetic retinopathy  ZETA-1 statistically significant results on ‘binocular 3-step worsening DRSS' endpoint provides a potential Phase 3 registration endpoint  Key Takeaways  Further analysis ​of ZETA-1 Phase 2 data, including insights for Phase 3 registration trial design   Plan for the EOP2 FDA meeting for APX3330 in DR indication  Data presentations at medical meetings  Advance APX3330 development (cGMP drug, NDA-enabling work, first Phase 3 trial, regional partnerships)  fully funded into 2025  Next Steps  To have a clinically meaningful impact on preventing progression to reduce likelihood of vision loss in diabetic retinopathy patients  Goal 
 

 Corporate Highlights   Ocuphire PharmaNasdaq: OCUP  Upcoming Catalysts:  Topline Results APX3330 ZETA-1 P2b trial for DR/DME (Early 2023)  EOP2 FDA Meeting for APX3330 (2H 2023)  Pivotal Phase 3 Trials for Nyxol in Presbyopia with 1st Data Readouts (Late 2023)  Potential Approval of 1st Nyxol NDA (Late 2023)  Two Lead Clinical-Stage Novel Drugs Addressing Multiple Large Ophthalmology Markets (~$20B US total) with Limited to No Competition & Patent Coverage to 2034+   1 As of close on January 24, 2023; 2 End of 3Q22 (10-Q); 3 Includes upfront payment from License Agreement   NDA submitted Nov 2022 for Nyxol’s first indication in RM   Global License Agreement Signed in Late 2022 with Viatris to Develop and Commercialize Nyxol for All Indications in the US and Globally   Successful Execution of 5 Trials in Last 2 Years with 6 Positive Phase 3 & Phase 2 Data Read-outs for Nyxol in RM, Presbyopia, and NVD   Strong Financial Position (with No Debt) to Support Operations into 2025 and Coverage from 5 Biotech Research Analysts   Stock Price1 $3.67  Market Cap1 $77M  Cash (Pro-Forma)2,3 ~$49 M   Shares Outstanding2 20.8M  Average Daily Volume ~200k Shares  Cash Runway Into 2025  APX3330 oral tablets  Diabetic Retinopathy/Diabetic Macular Edema (DR/DME) – diabetic eye disease  Nyxol preservative-free eyedrops  Reversal of Mydriasis (RM) – eye dilation  Presbyopia (P) – age-related blurry near vision  Night Vision Disturbances (NVD) – halos, glares, starbursts 
 

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