APX3330 Oral Tablet

ZETA-1 Phase 2 Trial in DR/DME Completed, Topline Results Reported Q1 2023, and End of Phase 2 Results Announced in Q4 2023

Ocuphire’s lead retinal product candidate, APX3330, is a first-in-class small-molecule inhibitor of Ref-1 (reduction oxidation effector factor-1 protein). Ref-1 is a regulator of transcription factors such as HIF-1a and NF-kB. Inhibiting REF-1 reduces levels of vascular endothelial growth factor (“VEGF”) and inflammatory cytokines which are known to play key roles in ocular angiogenesis and inflammation. Through inhibition of Ref-1, APX3330 normalizes the levels of VEGF to physiologic levels, unlike biologics that deplete VEGF below the levels required for normal function. APX3330 is an oral tablet administered twice per day for the treatment of diabetic retinopathy (“DR”). A Phase 2 study in subjects with DR and an End-of-Phase 2 meeting have recently been completed, and a Special Protocol Assessment is planned to be submitted with the U.S. Food and Drug Administration (FDA).

DR affects approximately 10 million people with diabetes and is projected to impact over 14 million Americans by 2050. DR is classified as Non-Proliferative Diabetic Retinopathy (“NPDR”), the early stage of the disease in which symptoms may be mild or non-existent or Proliferative Diabetic Retinopathy (“PDR”) which is the more advanced stage of diabetic eye disease that can be highly symptomatic with loss of vision. Approximately 80% of DR patients have NPDR that will progress to PDR if left untreated. Despite the risk for visual loss associated with this disease, over 90% of NPDR patients currently receive no course of treatment apart from observation by their eye care specialist until they develop sight-threatening complications. This is due to the treatment burden of the frequent eye injections required with currently approved therapies for this disease. APX3330 as an oral tablet has the potential to be an early, non-invasive treatment for the 8 million NPDR patients in the US. Treatment with APX3330 is expected to delay or prevent progression of NPDR, thereby reducing the need for expensive intravitreal injections with anti-VEGF therapies and reducing the likelihood of vision loss due to DR.

APX3330: 600mg Oral Dose

APX3330 is an investigational drug candidate that is being tested in clinical trials and has not yet been approved by the FDA or other regulatory agencies for commercial sale.

Comparison Graphic
Product Candidate Indication Development Stage Anticipated Milestones
Preclinical Phase 1 Phase 2 Phase 3 Regulatory Approval

Retina-Focused Development

APX3330 Oral Pill Diabetic Retinopathy (DR)/ Macular Edema (DME)
Preclinical complete
Phase 1 complete
Phase 2 in progress
Completed Trial
SPA Submission
Phase 3 not started
Regulatory Approval not started

EOP2 Mtg October 2023

Special Protocol Assessment (SPA) Submission

Multiple Indications with Large Market Potential

Given the progressive nature of these diseases and the need for repeated therapy, only a fraction of patients can sustain the initial improvement in vision seen with current therapies, highlighting the unmet need for better pharmacologic interventions. Earlier treatment options to prevent or delay vision loss for patients with diabetic eye disease are also important.

Diabetic Retinopathy

About Diabetic Retinopathy

Diabetes, a worldwide epidemic, is the leading cause of blindness among adults age 20-74. Diabetic retinopathy (DR) is a diabetes complication that affects the eyes, affecting over 10 million patients in the U.S. alone, in which chronically elevated blood sugar levels cause damage to blood vessels in the retina. There are two major types of DR:

  • Non-proliferative DR, or NPDR. NPDR is an earlier, more typical stage of DR and can progress into more severe forms of DR over time if untreated and if exposure to elevated blood sugar levels persists.
  • Proliferative DR, or PDR. PDR is a more advanced stage of DR than NPDR. It is characterized by retinal neovascularization and, if left untreated, leads to permanent damage and blindness.

When DR is in its early stages, blood vessels in the retina are damaged and can begin to leak fluid into the retina, a problem called diabetic macular edema (DME). In advanced stages, new and abnormal blood vessels form which may break and bleed. Fluid and hemorrhage interfere with vision and may further cause irreversible visual impairment due to retinal scarring and even retinal detachment. Even though biologic injection therapies have been approved for DR and treatment is possible, patients with DR are not widely treated in this early stage of the disease.

Market Landscape


U.S. prevalence

How APX3330 Can Help DR

We believe that APX3330’s oral delivery could be preferred over current invasive methods, and it has the potential to be used as monotherapy (non-proliferative or early proliferative stages of diabetic retinopathy) or as an adjunct therapy (advanced stages).

Diabetic Macular Edema

About Diabetic Macular Edema

Diabetic Macular Edema (DME) is a complication of DR where the macula swells with fluid leaked from the damaged blood vessels as a result of worsening diabetic retinopathy. It is one of the most common reasons for blindness in diabetics, affecting approximately 750,000 patients. DME may cause blurriness in the center of vision, the appearance of straight lines as wavy, colors that look dull or washed out, or blind spots. The pathogenesis of DME involves vascular leakage, retinal ischemia, and release of vasoproliferative growth factors and inflammatory mediators. Earlier treatment options to prevent or delay vision loss for patients with diabetic eye disease are important.

Market Landscape


U.S. prevalence

How APX3330 Can Help DME

APX3330’s safety profile, pharmacokinetic properties, molecular target engagement data observed in clinical trials, and drug exposure in the retina seen in mouse models, combined with a unique oral tablet formulation, suggest potential to reduce the frequency of anti-VEGF treatments and increase compliance for better outcomes.

Wet Age-related Macular Degeneration

About Wet Age-related Macular Degeneration

Age-Related Macular Degeneration (AMD) is a common eye condition affecting 11 million individuals in the U.S. and 170 million globally, mostly over the age of 55 years. It is a progressive disease affecting the central portion of the retina, known as the macula, which is the region of the eye responsible for sharpness, central vision, and color perception. Wet AMD (wAMD) is an advanced form of AMD characterized by neovascularization and fluid leakage under the retina. It is the leading cause of severe vision loss in patients over the age of 50 in the United States and EU. While wAMD represents only 10% of the number of cases of AMD overall, it is responsible for 90% of AMD-related severe vision loss. Untreated or undertreated wAMD results in further blood vessel leakage, fluid in the macula, and ultimately scar tissue formation, which can lead to permanent vision loss, or even blindness, as a result of the scarring and retinal deformation that occur during periods of non-treatment or undertreatment. Similar to severe DR and DME, current therapy for wAMD consists of intravitreal anti-VEGF injections, which have a number of side effects.

Market Landscape


U.S prevalence

How APX3330 Can Help wAMD

Based on APX3330 targeting Ref-1 and reducing VEGF production, it has potential use in wAMD. Further, to enter the wAMD injectable market, Ocuphire is considering the utility of second-generation product candidates of APX3330, such as APX2009 and APX2014, in intravitreal formulation.

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