Ophthalmology Pipeline Represents a Paradigm Shift in Treatment


  • Over 10M eye injections per year = Heavy treatment burden on patients and doctors
  • Approved and prospective drugs require a retinal ophthalmologist, a caregiver to drive to/from visits, and an expensive treatment


  • Patient administers drug at home with autoinjector subcutaneously up to once per month (potential for oral administration)
  • Market Research = > $3.5 B peak US sales
    • 51 US retinal ophthalmologists, 5 payers

    • Discount to Eylea, rebates, market access (conservative)

    • Patient market research ongoing

  • 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 activated cells in regions of inflammation
  • Crosses blood retinal barrier in monkeys, mice & rats
Selectively treating intracellular mechanisms of angiogenesis

D-4517.2: First-in-Class Home Administered Wet AMD Therapy

Mouse Laser CNV Model: Single Subcutaneous or Oral D-4517.2 Dose on Day 1

CNV Area (µm2) at Day 14

Once Every 2+ Weeks or Oral

  • D-4517.2 at 2 mg/kg (40 µg) subcutaneous (SC) dose equivalent to Eylea (aflibercept) intravitreal (IVT) dose (40 µg) at Day 14

  • Oral D-4517.2 doses equally or more effective

  • Human doses to achieve equivalent effect are safe and well tolerated

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


proprietary Sunitinib analog

D-4517.2: Safety Established in Healthy Humans

Phase 1, Single Dose – SC Doses Up to 1 mg/kg

Study Objectives:

Complete safety, PK, metabolism, clearance and safety of single SC dose administration in adult subjects

Study Results Summary:

  • Safe and well tolerated with only mild transient injection site reactions in a few patients (technique related)
  • No changes in safety labs
  • PK translates to effective doses in preclinical models

D-4517.2: Phase 2 Proof of Concept in Wet AMD and DME Patients

Two Stage Design

Stage 1 of Phase 2:

  • Safety, pharmacodynamics, and durability of subcutaneous D-4517.2 compared to Intravitreal aflibercept in wet AMD and DME Patients
    (Aflibercept to D-4517.2 crossover design in same patient) (30 patients)

Stage 2 of Phase 2:

  • Randomized, placebo/sham controlled, double masked non-inferior study comparing subcutaneous D-4517.2 to aflibercept (270 wet AMD patients)


  • Stage 1, Phase 2 LPI in 1H 2023

  • Stage 1, Phase 2 data in 2H 2023
  • Stage 2, Phase 2 FPI in 2024

Launch wet AMD Stage 2 and Separate DME Phase 2 in Parallel

Projected Product Launch = 2028

D-4517.2 Commercial Assessment

D-45172-Commercial Assessment