Ophthalmology

Ophthalmology Pipeline Represents a Paradigm Shift in Treatment

THE NEED

  • Over 10M injections per year = Heavy treatment burden on patients and doctors
  • Approved and pipeline drugs focus on duration of effect after intravitreal injection but still require a retinal ophthalmologist, a care giver to drive to/from visits, and an expensive treatment

OUR SOLUTION

  • Patient administers drug at home with autoinjector up to once per month (potential for oral administration)
  • Market expansion: > $1B product
    • 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

HD Targets Ocular Neovascularization After Systemic Dose

  • After systemic dose, uptake ONLY in inflammatory reactive cells
  • Crosses blood retinal barrier in monkeys, mice & rats

D-4517: First-in-Class Home Administered Wet AMD Therapy

Mouse Laser CNV Model: Single Subcutaneous or Oral D-4517 Dose on Day 1

Once Every 2+ Weeks or Oral

  • D-4517 at 2 mg/kg (40 µg) subcutaneous (SC) dose equivalent to Eylea (aflibercept) intravitreal (IVT) dose (40 µg) at Day 14
  • Oral D-4517 doses equally or more effective = >80x therapeutic window, minimal systemic exposure
  • HD uptake retinal neovascular genetic model (vldlr) with Campochiaro lab (JHU)

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

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