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Ocuphire Corporate Presentation November 2023
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 and approvals, pre-commercial activities, commercialization
strategy and timelines, business strategy, product labels, cash runway, scalability, future clinical trials in presbyopia (P), dim light/night vision disturbance (DLD) and diabetic retinopathy (DR) / diabetic macular edema (DME), including
the potential for Phentolamine Ophthalmic Solution (POS) to be a "best in class" presbyopia drop, and timing of planned future clinical trials for APX3330, APX2009 and APX2014, the advancement to Phase 3 registration path for APX3330, FDA
agreement on Special Protocol Assessment, the success and timing of planned regulatory filings, business strategy, cash runway, scalability, the potential for APX3330 to be the most advanced and the first line of therapy for DR patients, and
the potential market opportunity for and the ability of APX3330 to slow 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) changes in market opportunities, (viii) risks that the partnership with Viatris may not facilitate the commercialization or market acceptance of Ocuphire's product candidates; (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. Disclosures and Forward-Looking Statements
Ocuphire Pipeline Product Candidate Indication Pre-clinical Phase 1 Phase
2 Phase 3 Regulatory Approval Upcoming Milestones APX3330 Oral Pill Diabetic Retinopathy (DR) EOP2 Mtg October 2023 Special Protocol Assessment (SPA) Submission APX3330 Local Delivery Retina Select retinal drug delivery
technology APX2009 and APX2014 Local Delivery Retina Select retinal drug delivery technology Phentolamine Ophthalmic Solution 0.75% Eyedrops Pharmacologically-Induced Mydriasis APPROVED (RYZUMVI ) Sept 2023 Presbyopia (P) VEGA-2
Phase 3 Topline Data Q4 2023 Dim Light or Night Vision Disturbances (DLD) SPA Submitted LYNX-2 2nd Phase 3 trial (n=150+) SPA Submission Partnered with Viatris
Management Team with Decades of Drug Development Experience Drey ColemanVP,
Clinical Operations Amy Rabourn, CPA SVP, Finance Charlie Hoffmann, MBA SVP, Corporate Development Mitch Brigell, PhD Head, Clinical Development and Strategy Daniela Oniciu , PhD Global Head, R&D, Chemistry and Product
Development Ronil Patel, MTech, MS SVP, Operations and BD 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 George Magrath, MD, MBA CEO
Corporate Highlights Late-Stage Clinical Candidate for Retinal Diseases
Represents Multi-Billion Dollar Opportunity Phentolamine Ophthalmic Solution 0.75% (POS) for Refractive Disorders Global license agreement with Viatris to fund all development and commercialization for phentolamine indications: RYZUMVI
(Phentolamine Ophthalmic Solution) 0.75% for the treatment of pharmacologically-induced mydriasis received FDA approval in September 2023 Approval triggered $10M milestone payment Presbyopia and Dim Light Disturbances currently in Phase
3 Experienced Retina Drug Development Team to Advance APX3330 into Phase 3 APX3330: Paradigm Changing, Non-invasive, Safe Oral Tablet for millions of NPDR patients that are currently left untreated Ref-1, a novel, dual target
(angiogenesis and inflammation) for retinal diseases ZETA-1 Phase 2 showed APX3330 prevented or slowed progression of Diabetic Retinopathy (DR) Successful EOP2 meeting with the FDA and a Special Protocol Assessment (SPA) to be submitted
Diabetic Retinopathy Market and Unmet Need
Diabetic Eye Disease is a Common Cause of Blindness Diabetes and Diabetic
https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/symptoms-causes/syc-20351193 Two Types of DR Non-Proliferative Diabetic Retinopathy (NPDR) - most common form of DR - early stages of edema and exudates, blurred central
vision Proliferative Diabetic Retinopathy (PDR) - later stage of DR, marked by abnormal blood vessels and scar tissue on retina Diabetic Macular Edema (DME) can occur at any stage of DR Diabetes Mellitus is a group of diseases
characterized by high blood glucose levels. Diabetes results from defects in the body's ability to produce and/or use insulin Diabetic retinopathy (DR) occurs when fluctuations or instability in blood glucose levels damages blood vessels in
the retina Type 1 diabetes (T1D): The body produces very little or no insulin, which means that patients need daily insulin injections to maintain blood glucose levels Type 2 diabetes (T2D): The most common form of diabetes - either the
body does not produce enough insulin, or resists insulin Normal Retina Diabetic Retina
American Diabetes Association; International Diabetes Federation; Healthline;
*Ocuphire internal analysis and assumptions 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 Patient survey adapted from Lions
International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 Guidehouse Triangulation of Global Data, Market Scope and Investor Forecasts (2020) AMD = Age-Related Macular Degeneration; DME = Diabetic Macular Edema ;
BRVO = Branch Retinal Vein Occlusion National Center for Chronic Disease Prevention & Health Promotion. Health & economic costs of chronic diseases. Atlanta (GA): Centers for Disease Control & Prevention, US Department of Health
and Human Services; 2018 Four-Year Visual Outcomes in a Randomized Trial of Intravitreous Aflibercept for Prevention of Vision Threatening Complications of Diabetic Retinopathy (Protocol W)." JAMA. February 7, 2023 Diabetic Retinopathy at a
Glance Current Treatment Landscape Demonstrates Need for Non-Invasive Therapies The number of people with DR expected to increase more than 14M by 2050 There are ~8M adults in the U.S. with NPDR DR is the leading cause of blindness among
working-age adults with the median age of onset at 45 - 50 years Majority of moderate to severe patients with DR are not treated with anti-VEGF due to injection burden and no benefit to visual acuity Prevention of Progression is favored by
payors with chronic diseases such as diabetes which is the primary driver of increased healthcare costs Physicians have no non-invasive options for NPDR with current standard being wait-and-monitor
American Diabetes Association; International Diabetes Federation; Healthline;
*Ocuphire internal analysis and assumptions; Spherix Global Insights Patient survey adapted from Lions International Foundation and International Diabetes Foundation-Europe; Meltzer 2000 Estimates are provided by the National Eye Institute,
FactSheet, Global Data, and Research and Markets. Estimated values are rounded. Estimated prevalence in the U.S.; DME- Diabetic Macular Edema; Age-related Macular Degeneration; Geographic Atrophy; Retinal Vein Occlusion U.S Diabetic
Retinopathy Market Majority of the DR Patients are NPDR Severity Target Population for APX3330 10M Diabetic Retinopathy (DR) 34 Million Diabetics in US 8MNPDR Patients US Market Opportunity Target Patient
Population ~$6B+ 78% NPDR Non-Proliferative DR Proliferative DR Real-World Chart Review of DR Patients in US % of Patients Types of DR
Spherix Global Insights: DR Market DYNAMIX October 2022 Early treatment
diabetic retinopathy study research group. ophthalmology. 1991;98(5 suppl):823-33. Diabetes control and complications trial research group. N Engl J Med. 1993;329(14):997-86. Fathy C, Patel S, Sternberg P Jr, Kohanim S. Disparities in
adherence to screening guidelines for diabetic retinopathy in the United States: a comprehensive review and guide for future directions. Semin Ophthalmol. 2016;31(4):364-377. doi: 10.3109/08820538.2016.1154170 Progression of DR Severity
Measured up to 5 Years NPDR Patients are Rarely Treated with anti-VEGF Intravitreal Injections Due to Treatment Burden 1 Year Follow-up 3 Year Follow-up 5 Year Follow-up Percentage of Eyes that Worsen to PDR Regardless of severity, all
eyes worsen over time DR Severity (DRSS Score) Early Intervention with APX3330 can potentially slow the progression of Non-Proliferative Diabetic Retinopathy to Proliferative Diabetic Retinopathy
Diabetic Retinopathy Treatment Landscape
Current Standard of Care Based on Severity Currently, There Are No Non-Invasive
Treatments Approved for Early Intervention or Slowing the Progression Wait and Monitor for Progression Mild to Moderate NPDR Anti-VEGF
Injections PDR Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec 10 81-85 71-75 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec NPDR patients are monitored for progression requiring visits to the office every 4-6
months Gold standard Eylea and Lucentis injections are effective treatments in the first year for PDR 2021 ASRS PAT Survey
Landscape of Investigational Non-Invasive Therapies for Diabetic
Retinopathy Ocuphire's APX3330 is the Most Advanced Oral Drug Candidate Company Drug Target/MOA Indication Route of Administration Phase 1 Phase 2 Phase 3 Primary Endpoint/ Secondary Endpoints APX3330 Ref-1
inhibitor (Anti-angiogenesis & Anti-inflammatory) DR Oral 2022 2020: 2-step DRSS @wk24 RG7774 CB2 receptor (cannabinoid) DR Oral X 2023 2020: 2-step DRSS @wk36 BAY1101042 Guanylate Cyclase
activator DR Oral 2021: 2-step DRSS @wk24 OPL-0401 ROCK 1/2 inhibitor DR Oral 2021: 2-step DRSS @wk24 VX-01 AOC-3 inhibitor DR Oral 2022: Not Disclosed OTT166 Integrin inhibitor DR Eyedrop 2022:
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 is the ONLY
candidate with validated retinal pathways of angiogenesis and inflammation. Human exposure >10,000 subject days of systemic exposure at 600mg/day dose and a favorable safety and tolerability profile.
Landscape of Invasive Therapies (IVT/Suprachoroidal) for Diabetic Retinopathy
Eylea /Lucentis Approved, But Not Used in Patients with NPDR; Rarely Used in Mild PDR Company Drug Target/MOA Route of Administration Phase 1 Phase 2 Phase 3 Commercial Eylea (aflibercept) VEGF-A/B;
PIGF Intravitreal *1 Lucentis (ranibizumab) VEGF-A Intravitreal 2 KSI-301 (Tarcocimab) VEGF Intravitreal N/A EYP-1901 Voloronib (TKI) Intravitreal BI 764524 Anti-Sema3A Ischemia
modulator Intravitreal OTX-TKI Axitinib* (TKI) Intravitreal RGX-314 AAV8-VEGF Suprachoroidal (Gene Therapy) *Trials to Support Approval 1 Panorama Clinical Trial 2 Protocol I & T and Rise & Ride
Completed Ongoing X Discontinued * Failed as oral/systemic treatments in retina due to dose limiting toxicity Company websites and www.clinicaltrials.gov (as of October 31, 2023) Eylea is trademark of Regeneron and Lucentis is
trademark of Genentech
Logsdon et al (2018), Li et al (2014). APX3330 - Mechanism of Action Targeting
Ref-1 Inhibition Ref-1 Involved in Key Pathways that Contribute to Diabetic Retinopathy and Diabetic Macular Edema Ref-1 (reduction-oxidation effector factor-1) A novel target for retinal diseases, is a transcription factor regulator of
angiogenesis (VEGF) and inflammation (NFkB) Mechanism of Action - Ref-1 Inhibition Hypoxia Ref-1 HIF-1 VEGF (Signaling Cascade) Inflammation Ref-1 NF- B Other Growth Factors (Signaling
Cascade) TNF- Chemokines Neovascularization Lucentis EYLEA Anti-VEGF Steroids APX3330 Unique MOA decreases abnormal angiogenesis and inflammation APX3330 does not deplete the VEGF levels but rather normalizes VEGF levels to
physiologic levels Anti-VEGF injections do not target inflammation
APX3330: Drug Development History and Patents Significant Preclinical &
Clinical Data Supporting Human Safety, MOA, and PK 12* Phase 1 & Phase 2 Trials Exposure in Humans >10,000 Subject Days at 600mg/day Patents to2035+ Studied in inflammation/hepatitis & cancer patients (Studied by Eisai
& Apexian, respectively) APX3330 New Chemical Entity Preclinical Efficacy & Toxicology Package APX3330 IND 6 Phase 1 Trials 5 Phase 2 Trials Phase 2 Trials Phase 3 Registration NDA Filing Focus on Ophthalmology Includes
ZETA-1 trial Previously developed by Eisai for hepatic inflammatory indications and by Apexian for solid tumors in 11 Phase 1 and 2 trials Extensively studied in over 20 in-vitro and animal studies with favorable efficacy and safety
Tao Yan et al. APX3330 Promotes Neurorestorative effects after stroke in type
one diabetic rats. Aging and Disease. Vol 9, Oct 2018 Apurinic/Apyrimidinic endonuclease 1 regulates inflammatory response in macrophages. Jedinak A, Dudhgaonkar S, Kelley MR, Sliva D. Anticancer Res. 2011 Feb;31(2):379-85. PMID:
21378315 Fehrenbacher, J. C., Guo, C., Kelley, M. R. & Vasko, M. R. DNA damage mediates changes in neuronal sensitivity induced by the inflammatory mediators, MCP-1 and LPS, and can be reversed by enhancing the DNA repair function of
APE1. Neuroscience 366, 23-35, doi:10.1016/j.neuroscience.2017.09.039 (2017) In-vitro Validation of Mechanism of Action APX3330 Reduces VEGF levels and Inflammatory Cytokines; Provides Neuronal Protection APX3330 reduces VEGF protein
expression in preclinical stroke model APX3330 reduces pro-inflammatory cytokines in LPS stimulated macrophages Increasing APX3330 dose VEGF Control APX3330 APX3330 enhances Ref-1 endonuclease activity in dorsal root ganglion
neurons APX3330 increases DNA oxidative repair and neuronal protection
APX3330 VEGF Effects in Normal Cells Abnormal Conditions (e.g.,
hypoxic): Increased level of VEGF activity Normal Conditions: Physiological level of VEGF activity Kamba 2007; Girardi 2010; Li 2014 APX3330 Investigator Brochure Biologic Anti-VEGF Treatment APX3330 Anti-Ref-1 Treatment Biologic
anti-VEGF agents inactivate VEGF directly and reduce VEGF levels below normal levels Inhibition of Ref-1 by APX3330 returns VEGF levels to normal levels VEGF is a growth factor that is necessary for normal function of multiple cell types
including vascular endothelium and neurons By returning VEGF levels to normal, APX3330 can reduce neovascularization, vascular leakage and the inflammatory response without adverse systemic effects The safety profile of APX3330 to date
has not shown any of the adverse effects that has been seen with systemic administration of anti-VEGF biologics such as cardiovascular pathology, hypertension, arteriothrombotic events, or renal dysfunction APX3330 ARPE-19 cell
line APX3330 prevents VEGF overproduction in ARPE-19 cells APX3330 Restores Normal Levels Unlike Biologic Anti-VEGFs that Reduce VEGF Below Normal
APX3330 ZETA-1 Clinical Trial
ZETA-1: Phase 2 Trial of Oral APX3330 in Subjects With Diabetic
Retinopathy Multi-center, Randomized, Double-Masked, Placebo-Controlled 24-Week Trial Primary: % subjects with 2 step improvement on DRSS (Diabetic Retinopathy Severity Scale1) at week 24 Secondary: DRSS improvement 1, 2, 3, 4
study eye, fellow eye, binocular DRSS worsening 1, 2, 3, 4, study eye, fellow eye, binocular Progression to vision threatening complications Central subfield thickness (CST) Best Corrected Distance Visual Acuity (BCDVA) DME fellow