Target Disease: Retinal Diseases

The retina is a neuronal tissue located at the back of the eye. Its primary function is the perception of light, the processing of light induced stimuli, and the transmission of light-dependent information to the brain.

Retinal diseases like wet age-related macular degeneration (wet AMD), diabetic retinopathy (DR) and geographic atrophy (GA) can lead to permanent vision loss. VEGF is a protein produced by cells which stimulates the formation of new abnormal blood vessels, a process called neovascularization, and induces vascular permeability, leading to leakage and swelling of the retina. Swelling of the retina leads to vision decline and death of the retinal cells, which can irreversibly cause blindness if not adequately treated.

In addition, a large number of hereditary diseases affect the retina and can result in severe vision impairment or blindness.

Inherited Retinal Diseases

About Inherited
Retinal Diseases (IRDs)

Grouped under the term “inherited retinal degeneration” diseases such as Retinitis Pigmentosa (RP), Leber’s congenital amaurosis (LCA), and Stargardt’s disease (STGD) often result in the degeneration and loss of the light-sensitive cells in the retina, called photoreceptors, leading to visual impairment and blindness.
Grouped under the term “inherited retinal diseases”, Retinitis Pigmentosa (RP), Leber’s congenital amaurosis (LCA), and Stargardt’s disease (STGD) often result in the degeneration and loss of the light-sensitive cells in the retina, called photoreceptors, leading to visual impairment and blindness.
The most common IRDs are caused by a genetic defect in a single gene, out of more than 280 possible genes, which compromises the viability of photoreceptors and leads to photoreceptor cell death.
Patients with these conditions may develop symptoms in early childhood, including night blindness or the inability to see segments of the world in front of them. They can take abnormally long periods of time to adjust to changes in lighting, and some patients may even find lights uncomfortable. Eventually, most individuals with IRD will lose most of their sight.
Normal Retina
Photoreceptors in a healthy retina. There are two general types of photoreceptors, called rods and cones. Rods are in the outer regions of the retina and allow us to see in dim-light conditions. Cones reside mostly in the central portion of the retina and allow us to perceive fine visual detail and color.
Retina affected by RP
Retina affected by RP shows a degeneration of the rods usually followed by a secondary degermation of cones, eventually leading to complete blindness.

Unmet Needs of Patients
with Inherited Retinal
Diseases

The death of photoreceptors due to IRDs results in permanent vision loss or blindness. All but one of these diseases are still untreatable today.

To date, only one drug has been approved to address a single mutation (RPE65), which accounts for a very small fraction of IRDs, leaving the vast majority of patients without therapeutic options.

cGMP ANALOG MECHANISM OF
ACTION




This graphic illustrates how GB-601 is thought to inhibit the cGMP cascade leading to photoreceptor cell death.


Genetic defects in many different retinal degenerative (RD) genes lead to high levels of cGMP, which over-activate protein kinase G (PKG) and cyclic nucleotide gated channel (CNG channel). While CNG channel function is required for vision (i.e., normal physiology), over-activation of PKG causes photoreceptor cell death (i.e. pathophysiology). GB-601 reduces excessive PKG activity and increases photoreceptor survival.







Genetic defects in many different retinal degenerative (RD) genes lead to high levels of cGMP, which over-activate protein kinase G (PKG) and cyclic nucleotide gated channel (CNG channel). While CNG channel function is required for vision (i.e., normal physiology), over-activation of PKG causes photoreceptor cell death (i.e. pathophysiology). GB-601 reduces excessive PKG activity and increases photoreceptor survival.
Graybug is developing these cGMP analogs as first-in-class, mutation-agnostic long-acting therapeutics to treat hereditary retinal diseases covering a broad range of mutations. GB-601 is in early-stage development.
Explore Our Pipeline