Our Science

Early Intervention
to Prevent Progressive Ocular Disease

Vision loss is a rapidly growing cause of disability, globally affecting all age groups, from the premature infant to age-related conditions. Progressive corneal conditions may lead to irreversible scarring with vision loss. Progressive retinal conditions cause loss of retinal neurons, including ganglion cells and sensory cells and, once lost, cannot be replaced.

Neuroprotectin D1 (NPD1), the eye’s most powerful protective homeostatic regulator, is an evolutionary adaption to protect the eye during normal conditions.

NPD1 is a highly potent lipid derived small molecule agonist. Activating multiple regulatory pathways aimed at tissue protection NPD1 has the therapeutic advantage of targeting pathological redundancy.

Anida is developing AP-001, a slightly modified version of NPD1. AP-001 shows excellent therapeutic activity in established translational models of corneal and retinal disease and ocular tissue distribution supporting its development as eye drop for both corneal and retinal indications.

Therapeutic eye drop delivery is currently limited to corneal disease but requires frequent administration due to rapid drug elimination in the eye. The need of repeat administration together with limited drug distribution to the back of the eye has prevented development of eye drops as an effective route to treat retinal conditions.

The particular physiochemical properties of AP-001 allow the targeting of both corneal and retinal indications delivered as an eye drop and demonstrated in large eye model. Combined with its long duration of action once or twice daily clinical administration is anticipated.

The lasting effect of AP-001 indicates a favorable dissociation between duration of effect and need for continuous exposure in the target tissue and is ideal for an eye drop. AP-001 as potent agonist represents a major advantage over antagonists and inhibitors that continuously need to engage targets for full efficacy.

Retina

Our current understanding of ROP, DRD, and AMD indicates the need of early multi-targeting to prevent disease progression. As an agonist AP-001 in a single molecule broadly targets inflammation, directly inhibits free radical formation, and through additional pathways is neuroprotective by controlling apoptosis and necroptosis, while activating resolution and survival pathways to preserve tissue integrity.

(ROP: retinopathy of prematurity; DRD: diabetic retinal disease; AMD: age-related macular degeneration)

Neovascularization

Neovascularization

Retina microglia

Retina microglia

AP-001, once daily eye drop, reduces pathological blood vessel formation in the retina (red) and is associated with microglia shape change from proinflammatory to proresolution (green). AP-001 upstream regulates VEGFA, TNF, miR-132, miR-155 and IL-17 which all contribute to neovascular pathology.
AP-001 is further shown to promote normal blood vessel formation.

Cornea

Progressive ocular surface diseases commonly have a complex pathology in an interplay between the corneal epithelium, corneal sensory innervation, and immune cells. Central to several conditions is the loss of corneal sensory innervation and its necessary trophic support of corneal integrity. However, concurrent with attempts at reinnervation stimulation of reepithelialization and control of inflammation will accelerate resolution, and relevant in neurotrophic keratopathy, diabetic corneal disease and severe forms of dry eye disease.

AP-001 eye drop administration for 6 weeks results in corneal reinnervation associated with sensory restitution

AP-001 in corneal translational research:

  • Stimulated corneal sensory reinnervation following partial corneal denervation in the rabbit (see above)
  • Equally effective to nerve growth factor (NGF) in stimulating trigeminal neurite outgrowth
  • Equally effective to epithelial growth factor (EGF) in closing epithelial defects; healing confirmed in vivo
  • In model of herpes simplex virus-1 (HSV-1) infection prominently dampened inflammation and reduced keratitis