Slide 1: Ocuphire KOL Event: APX3330
Ocuphire KOL Event: APX3330 October 14, 2022
Slide 2: Disclosures and Forward-Looking Statements
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,
Slide 3: APX3330 KOL Event: Agenda & Speakers
Ocuphire APX3330 KOL Event: Agenda & Speakers Speakers Speakers Agenda Time (EDT) Mina Sooch, MBA President & CEO and Founder Introductions & Company Overview 11:00 am – 11:10 am Caroline Baumal, MD Disease of Diabetic Retinopathy 11:10 am – 11:20 am Peter Kaiser, MD Current DR/DME Treatment Landsca
Slide 4: Agenda & Speakers (continued)
Speakers Agenda Time (EDT) ZETA-1 Trial Design and Data Expectations 12:00 pm – 12:15 pm Q&A Closing Remarks Q&A Moderator: Corey Davis, PhD 12:15 pm – 12:30 pm Ocuphire APX3330 KOL Event: Agenda & Speakers Peter Kaiser, MD Caroline Baumal, MD David Lally, MD Mina Sooch, MBA Peter Kaiser, MD Carolin
Slide 5: Company Overview
Company Overview Presenter: Mina Sooch, CEO and Founder of Ocuphire Pharma Over 25 years of pharmaceutical and biotech experience as CEO, entrepreneur, venture capitalist, and strategy consultant Successful track record of hundreds of millions of capital raised for leading private/public biotech com
Slide 6: Upcoming Catalysts in 4Q22
Upcoming Catalysts in 4Q22: Topline Results APX3330 ZETA-1 P2b trial for DR/DME NDA Filing for Nyxol for RM P = Presbyopia RM = Reversal of Mydriasis NVD = Night Vision Disturbances DR/DME = Diabetic Retinopathy/Diabetic Macular Edema Ocuphire PharmaNasdaq: OCUP Founded in 2018, Acquired 2 Lead Asse
Slide 7: Ocuphire Overview: Two Late-Stage Clinical Assets
Ocuphire Overview Two Late-Stage Clinical Assets Addressing Unmet Needs in Multiple Large Markets 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 Pate
Slide 8: Track Record of Achieving Milestones
Track Record of Achieving Milestones Multiple Positive Data Readouts with Multiple Catalysts Ahead Ongoing Partnering Discussions with Leading Ophthalmic Companies (including Europe and Asia) 2021 – 1H 2022 2H 2022 – 2023 Submit Nyxol NDA for RM Report APX3330 Phase 2b Data for DR/DME (ZETA-1) Initi
Slide 9: Disease of Diabetic Retinopathy
Disease of Diabetic Retinopathy Presented by: Caroline Baumal, MD Professor of Ophthalmology at Tufts Medical Center Co-Director of the Retina Service and Medical Retina Fellowship at New England Eye Center Authored over 170 publications, 33 book chapters on retinal diseases, and edited the book Tre
Slide 10: Diabetic Eye Disease is Common Cause of Blindness
Diabetic Eye Disease is Common Cause of Blindness Diabetes and Diabetic Retinopathy (DR) https://webeye.ophth.uiowa.edu/eyeforum/tutorials/diabetic-retinopathy-med-students/Classification.htmhttps://www.mayoclinic.org/diseases-conditions/type-1-diabetes/symptoms-causes/syc-20353011 https://www.mayoc
Slide 11: Diabetes is a Growing Global Health Epidemic
Diabetes is a Growing Global Health Epidemic Diabetes Cost Burden Over $900 Billion Dollars in Worldwide Health Expenditure Source: International Diabetes Federation, Diabetes Atlas 10th Edition, 2021, https://diabetesatlas.org/atlas
Slide 12: Diabetic Patients Usually Present with Complex Co-Morbidities
Diabetic Patients Usually Present with Complex Co-Morbidities Diabetic Patients are Young and Face Life-long Systemic and Ocular Complications 1. Petrella RJ, et al. J Ophthalmol 2012;159167; 2. International Diabetes Federation, Diabetes Atlas 6th Edition, http://www.idf.org/diabetesatlas; 3. Natio
Slide 13: Global Prevalence of Diabetes-Associated Retinal Disease
DR: 11M* DME: 7M* DR: 16M* DME: 6M* DR: 4M* DME: 4M* DR: 7M* DME: 4M* DR: 18M* DME: 8M* DR: 15M* DME: 5M* DR: 32M* DME: 14M* USA DR: 8M2 DME: 0.75M2 North America & Caribbean Global Prevalence of Diabetes-Associated Retinal Disease DR Affects 1 in 3 People with Diabetes; DME Affects 1 in 13 People w
Slide 14: Measuring the Severity of Diabetic Retinopathy
Measuring the Severity of Diabetic Retinopathy DRSS is Regularly Used For FDA Approvals; Not As Widely Used in Everyday Practice Arcadu, F., Benmansour, F., Maunz, A. et al. Deep learning algorithm predicts diabetic retinopathy progression in individual patients. npj Digit. Med. 2, 92 (2019). https:
Slide 15: DRSS Predicts Vision-Threatening Complications
DRSS Predicts Vision-Threatening Complications (PDR/DME) Percent of Eyes Progress to PDR at 1-Year, 3-Year, and 5-Year Visits by Baseline DR Severity Early treatment diabetic retinopathy study research group. ophthalmology. 1991;98(5 suppl):823-33. Diabetes control and complications trial research g
Slide 16: Vision Loss is #1 Concern of Diabetic Patients
Vision Loss Other Eye Problems Amputation, Losing a Leg Cardiovascular/Heart Problems Foot Problems Kidney Problems Vision Loss is #1 Concern of Diabetic Patients Diabetic Retinopathy is a Progressive Vision-Threatening Disease Source: Patient survey adapted from Lions International Foundation and I
Slide 17: Early Management of Diabetic Retinopathy
Early Management of Diabetic Retinopathy Poor Adherence to Medical Management and Lifestyle Options Worsen DR Source: Zhang X et al. Cell Biosci. 2014;14:4:27 Control of Blood Sugar Control of Blood Pressure Smoking Cessation Control of Lipids Medical and lifestyle management is first line of treatm
Slide 18: Majority of Physicians Use a Wait and Monitor Approach
Majority of Physicians Use a “Wait and Monitor” Approach for DR Patients Over 90% of DR Patients Are Not Treated Proactively and Anti-VEGF Use is Limited Source: ASRS 2021 Preferences and Trends (PAT) Survey How do physicians treat patients with severe NPDR without DME? Closely monitor retinopathy a
Slide 19: Diabetic Retinopathy At a Glance
Diabetic Retinopathy At a Glance Current Treatment Landscape Demonstrates Need for Less Invasive Therapies Source:1. American Diabetes Association; International Diabetes Federation; Healthline; *Ocuphire internal analysis and assumptions; 2. Das UN. DME, retinopathy and age-related macular degenera
Slide 20: Current DR/DME Treatment Landscape
Current DR/DME Treatment Landscape Presented by: Peter Kaiser, MD Chaney Family Endowed Chair in Ophthalmology Research, Professor of Ophthalmology, Cleveland Clinic Lerner College of Medicine and Cole Eye Institute Clinical research expert, serving as a Study Chairman of 5 major, multi-center, inte
Slide 21: Anti-VEGF Therapies are Standard of Care for AMD/DME
2004 2006 2011 2012 Ranibizumab nAMD 2014 2019 Aflibercept DME 2022 MOA focused on VEGF and local delivery have demonstrated efficacy for approved treatments, are the current standard of care, and have been highly effective for wAMD/DME. However, these therapies have limited use in DR AfliberceptnAM
Slide 22: Panorama Study Emphasizes Need for Proactive Treatment of NPDR
Panorama Study Further Emphasizes Need for Proactive Treatment of NPDR Eyes Treated with Aflibercept Showed a >2-step Improvement in DRSS Level at 24 and 52 Weeks Brown DM, Wykoff CC, Boyer D, Heier JS, Clark WL, Emanuelli A, Higgins PM, Singer M, Weinreich DM, Yancopoulos GD, Berliner AJ, Chu K, Re
Slide 23: AAO Preferred Practice Pattern Reveals High Unmet Need in NPDR
AAO-Preferred Practice Pattern Reveals High Unmet Need in Mild, Moderate, and Severe NPDR Patients Unmet Need Remains High in Mild, Moderate and Severe NPDR Patients Source: Diabetic Retinopathy Preferred Practice Pattern – AAO 2019; LTFU: Lost To Follow-up; IVT: Intravitreal Injections; PRP: Panret
Slide 24: Current Conventional Treatment is Challenging for Patients
Current Conventional Treatment is Challenging for Patients Access and Time Burden are Further Barriers for DR Patient Compliance Lu AJ, et al. Analysis of patient-reported barriers to diabetic retinopathy follow-up. Ophthalmic Surg Lasers Imaging Retina. 2019;50(2):99-105. Prenner J et al. Am J Opht
Slide 25: Multiple Targets in DME/DR Treatment Landscape
Multiple Targets in DME/DR Treatment Landscape Anti-VEGF Therapy is Mainstay, but Under/Non-Responders Remain, and Early Treatment is Limited https://www.reviewofophthalmology.com/article/a-peek-into-the-diabetic-retinopathy-pipeline Longer Duration IVTs Extended Release Combination Therapies Oral T
Slide 26: Intravitreal Injections Landscape (DR patients)
Intravitreal Injections Landscape (DR patients) Eylea/Lucentis Approved, But Not Used in Patients with Mild NPDR and Mild PDR Company websites; www.clinicaltrials.gov Company Drug Target/MOA Route of Administration Phase 1 Phase 2 Phase 3 Commercial Eylea (aflibercept) VEGF-A/B; PIGF Intravitreal ✓
Slide 27: Topical Eyedrops in Clinical Development for DR/DME
Topical Eyedrops in Clinical Development for DR/DME Inflammation MOAs in Phase 2 with Novel Eyedrops Company websites; www.clinicaltrials.gov Company Drug Target/MOA Indication Route of Administration Phase 1 Phase 2 Phase 3 Commercial OCS-01 Steroid DME Eyedrop ✓ ✓ OTT166 Integrin inhibitor DR Eyed
Slide 28: Oral Treatments in Clinical Development (DR)
Oral Treatments in Clinical Development (DR) Most Drugs Target Only Inflammation Company websites; www.clinicaltrials.gov Most Drugs Target Only Inflammation Company Drug Target/MOA Indication Route of Administration Phase 1 Phase 2 Phase 3 LY333531 Protein Kinase C inhibitor DR Oral ✓ ✓ X 2006 APX3
Slide 29: APX3330 is Different Than Past Oral Failures in Retina
APX3330 is Different Than Past Oral Failures in Retina APX3330 Targets Dual, Validated Retinal Disease Pathways with Favorable Human Safety Data Bhatwadekar 2020 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265898/pdf/nihms-1594067.pdf Bryant 2009 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC490571
Slide 30: Opportunities for New Therapies in Retina
New MOAs/therapies are needed to: Provide non-invasive options for early disease management Decrease in Diabetic Retinopathy Severity Score (DRSS) Decrease in macular edema Reduce vision threatening complications (VTC) Improve in macular ischemia Improve compliance by longer acting drugs Manage infl
Slide 31: APX3330: Paradigm Shift Oral Treatment Option
APX3330: Paradigm Shift Oral Treatment Option Presented by: David Lally, MD Director of the Retina Research Institute at New England Retina Consultants Retina Surgeon at Baystate Medical Center Assistant Professor of Ophthalmology at the University of Massachusetts Medical School-Baystate Published
Slide 32: APX3330 – Novel and Dual-Acting MOA in an Oral Pill
APX3330 – Novel and Dual-Acting MOA in an Oral Pill Ref-1 Involved in Multiple Key Pathways that Contribute to Diabetic Retinopathy and DME Logsdon et al (2018), Li et al (2014). Rangasamy S, McGuire PG, Das A. Middle East Afr J Ophthalmol 2012;19:52–59; Sohn HJ et al. Am J Ophthalmol 2011;152:686–6
Slide 33: In Vitro Validation of APX3330 Mechanism of Action
In Vitro Validation of APX3330 Mechanism of Action APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type one diabetic rats. Aging and Disease. Vol 9, Oct 2018 Apurinic/Apyrimidinic endonuclea
Slide 34: APX3330 Restores Normal VEGF Levels
Abnormal Conditions (e.g., hypoxic): Increased level of VEGF activity Normal Conditions: Physiological level of VEGF activity APX3330 VEGF Effects in Normal Cells APX3330 Restores Normal Levels Unlike Biologic Anti-VEGFs that Reduce VEGF Below Normal Kamba 2007; Girardi 2010; Li 2014; APX3330 Invest
Slide 35: APX3330 Preclinical & IND-Enabling Studies Completed
APX3330 Preclinical & IND-Enabling Studies Completed Over 20 Clinical Trials Across Healthy, Hepatic and Cancer Patients Extensively Evaluated in Over 20 Studies by Large Japanese Pharma Eisai Toxicology Studies PK, Absorption, Distribution, & Excretion Studies Safety Pharmacology Studies Geno Tox,
Slide 36: Preclinical Data: Oral APX3330 Blocks Neovascularization
Silva et al. ARVO 2021 Annual Meeting *Published data on EYLEA. This study was performed independently from APX3330 study and is a cross-study comparison. **Li 2014; *** Pasha 2018; ****Jiang 2011 (Vldlr -/- : Very Low-Density Lipoprotein receptor knock-out mice) Preclinical Data: Oral APX3330 Block
Slide 37: Summary of APX3330 Prior Clinical Trials
Summary of APX3330 Prior Clinical Trials Completed 11 Clinical Trials Across Healthy, Hepatic and Cancer Patients Phase 1 Study ID Patient Population Treatment Groups APX_CLN_0001 Healthy Subjects APX3330, Placebo APX_CLN_0002 Healthy Subjects APX3330, Placebo APX_CLN_0003 Healthy Subject
Slide 38: PK Data Supporting the ZETA-1 Trial
Phase 1 Clinical Trials: PK Data Supporting the ZETA-1 Trial APX3330 has Oral Bioavailability and a Sustained PK Profile Apexian preclinical data (unpublished) APX3330 Investigator Brochure Eisai PK clinical data APX_CLN_0002 Favorable Oral Bioavailability Sustained Pharmacokinetic Profile Tmax 3-4
Slide 39: Safety Summary From Phase 1 and Phase 2 Trials
Phase 1 and Phase 2 Clinical Trials performed by Eisai and Apexian Safety Summary From Phase 1 and Phase 2 Trials Low AEs Across 11 Trials, <5% Mild Drug Related AEs, Discontinuations Similar Across Arms Totals Across ALL Phase 1 and Phase 2 Studies (Among Healthy Subjects, Hepatitis Patients, and O
Slide 40: ZETA-1 Phase 2b Trial in Diabetic Retinopathy
ZETA-1 Phase 2b Trial in Diabetic Retinopathy Presented by: David Lally, MD David Lally, MD Jefferson Medical College
Slide 41: ZETA-1 Phase 2b Design for DR/DME
ZETA-1 Phase 2b Design for DR/DME Ongoing, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial (Similar To Eylea P3 DR Trial) NPDR = non-proliferative diabetic retinopathy (which includes non centrally involved diabetic macular edema) PDR = proliferative diabetic retinopathy (which includes
Slide 42: Key Eligibility Criteria in ZETA-1
Source: ZETA-1 trial Key Eligibility Criteria in ZETA-1 Oral Medication Provides Binocular Treatment; DME Allowed in Fellow Eye
Slide 43: Why DRSS is an Important Endpoint?
Why DRSS is an Important Endpoint? FDA Accepted Endpoint for EYLEA® in PANORAMA Pivotal DR Trial - 2 Step Improvement on the DRSS Score Eylea® Panorama study Diabetic Retinopathy Severity Scale (DRSS)
Slide 44: ZETA-1 Trial: Demographics and Masked Safety Data
ZETA-1 Trial: Demographics and Masked Safety Data Presented by: Caroline Baumal, MD Caroline Baumal, MD University of Toronto
Slide 45: Baseline Characteristics for ZETA-1 Trial
Baseline Characteristics for ZETA-1 Trial Typical Demographics for Diabetic Population Source: ZETA-1 Demographics and Baseline Characteristics Parameter Total N = 103 Age (years): mean (range) 56 (24-81) Sex: n (%) Male 50 (49%) Female 53 (51%) Race: n (%) American Indian or Alaskan Native 4 (4%) A
Slide 46: Baseline Characteristics for ZETA-1 Trial (Continued)
Baseline Characteristics for ZETA-1 Trial (Continued) DRSS Scores in Diabetic Study Population Source: ZETA-1 Demographics and Baseline Characteristics Parameter Total N = 103 Total N = 103 Study Eye DRSS n(%) DRSS 47 (Moderately Severe NPDR) 39 (38%) DRSS 53 (Severe NPDR) 53 (52%) DRSS 61 (Mild PDR
Slide 47: Baseline Characteristics for ZETA-1 Trial (Continued)
Baseline Characteristics for ZETA-1 Trial (Continued) Key Visual Metrics in Diabetic Study Population Source: ZETA-1 Demographics and Baseline Characteristics * N=102 due to a fellow eye not being graded. Parameter Total N = 103 Study Eye Screening CST (um): mean (range) 270 (203-319) Fellow Eye Scr
Slide 48: Comprehensive Laboratory Panels Collected in ZETA-1
Comprehensive Laboratory Panels Collected in ZETA-1 Blood, Kidney, and Inflammatory Markers Evaluated Chemistry Albumin Alanine aminotransferase (ALT) Alkaline Phosphatase Aspartate aminotransferase (AST) Blood Urea Nitrogen (BUN) Creatinine Glucose (Random) Sodium Total bilirubin Total protein Test
Slide 49: Masked Safety Findings from Ongoing ZETA-1 Trial
Masked Safety Findings from Ongoing ZETA-1 Trial Favorable Safety Profile (as of 9/15/2022) Observed with 600 mg Oral Daily Doses in Diabetic Subjects 1. 12 events in 8 subjects: diarrhea, worsening DME (OD and OS), pruritis, urticaria, blurry vision, decrease in hemoglobin level, ischemic diabetic
Slide 50: APX3330 Product Candidate Profile for Multiple Retinal Indications
APX3330 Product Candidate Profile for Multiple Retinal Indications Oral, First-In-Class Ref-1 Inhibitor with Favorable Human Safety Data *11 completed Phase 1 and Phase 2 clinical trials by Eisai and Apexian; along with ongoing ZETA-1 trial by Ocuphire (*includes ~103 subject) Novel MOA for treating
Slide 51: ZETA-1 Trial Design and Data Expectations
ZETA-1 Trial Design and Data Expectations
Slide 52: APX3330 has the Potential to be First Line of Therapy for DR Patients
APX3330 has the Potential to be First Line of Therapy for DR Patients Eylea® label; APX3330 Investigator Brochure, ZETA-1 clinical trial Clinically meaningful decrease in diabetic retinopathy severity with APX3330 Early intervention with oral may reduce progression to vision threatening DR into DME
Slide 53: APX3330 is Positioned to Fulfill a Significant Unmet Need in Diabetic Eye Disease
APX3330 is Positioned to Fulfill a Significant Unmet Need in Diabetic Eye Disease Favorable PK and safety data from clinical trials and overall masked safety data supports a potential oral treatment for diabetics with DR/DME Dual mechanism of action may benefit inflammation from co-morbidities DR/DM