D-4517.2

Ophthalmology Pipeline Represents a Paradigm Shift in Treatment

THE NEED

  • 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

OUR SOLUTION

  • Patient administers drug at home with autoinjector subcutaneously 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
nanomolar binding to repair Receptor Tyrosine Kinases

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

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

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

D-4517

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)
 

TIMELINES

  • Stage 1, Phase 2 FPI in Q2 2022
  • Stage 1, Phase 2 LPI in Q4 2022
  • Stage 2, Phase 2 FPI in Q3 2023

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