Ophthalmology

Age-related macular degeneration (AMD) is a common degenerative disease of the retina, the light-sensitive tissue in the back of the eye.

Wet AMD occurs when abnormal blood vessels (choroidal neovascularization) grow underneath the macula leading to leakage of fluid and blood leading to visual distortion and acute vision loss. If untreated or undertreated, wet AMD leads to scar formation and permanent damage that results in blindness.

Even with approved treatments, significant unmet needs persist related to the following:

  • Poor Compliance: This is driven through a combination of patient fatigue with chronic intravitreal injections as well as their caregivers (generally a family member) to consistently take time away from work or other duties in order to drive the patient to the ophthalmologist for their treatment and follow-up appointments.
  • Accessibility: Despite the increased burden of retinal disease, the distribution and practice patterns in the United States places significant non-clinical barriers to treatment. Patients living in underserved markets are at higher risk for vision loss because their physical location places them at a geographic disadvantage to large metropolitan areas and more affluent suburbs with a higher concentration of retinal ophthalmologists to provide treatment, further underscoring the value of a product that could be administered by the patient at home.

Our Approach

  • Patient administers drug at home with autoinjector up to once per month
    (potential for oral administration)

Market Expansion

  • Patients in rural areas receive convenient treatment (especially parts of China and India)
    • Diabetic patients maintain compliance (treated for decades)
    • Treatment of earlier stage of AMD
  • Lower cost – manufactured at up to 1/10 the cost of other approaches

We have designed and optimized an HDT that:

  • Precisely targets reactive macrophages and retinal pigment epithelial cells (RPEs) after systemic administration
  • Preclinical models of neovascularization suggest the potential for a superior product profile
    • The HD is retained within the CNV lesion of ocular neovascularization for >30 days supporting  an optimal dosing and administration profile
    • Potential for superior efficacy compared currently approved biologics requiring intravitreal administration at a physician’s office

Laser-induced CNV Mouse Model

D-4517 Alters Pharmacology through Non-Cleavable Dendrimer

Sunitinib (Sutent™) D-4517
Liver toxicity (decreased size/increased ALT/AST) No observed effect
Proteinuria, decrease in kidney size (males) No observed effect
Hypoglycemia (females) No observed effect
Decrease in heart size (males) No observed effect

Same sunitinib exposure in both groups

D-4517

proprietary Sunitinib analog