Our lead candidate OCX063 is a small molecule drug that targets a novel receptor in the eye, which has been previously shown to mediate diverse signalling pathways associated with inflammation and fibrosis in the development and progression of fibrotic diseases of the kidney, heart, lung, and intestine. OCX063 is initially being developed for inflammation and fibrosis in the back of the eye, in ocular conditions such as DR and wet AMD.
OCX071 is our second candidate, which has been demonstrated to prevent retinal inflammation at the back of the eye in DR. OCX071 is being investigated for the treatment of ocular inflammation and fibrosis in the front of the eye, including dry eye syndrome and ocular graft versus host disease.
Diabetic retinopathy (DR) is a common complication of diabetes and remains one of the leading causes of severe vision loss in adults. DR affects almost all individuals with type 1 diabetes and more than 60% of those with type 2 diabetes within 20 years of living with diabetes.
DR is a progressive eye disease that worsens over time as the result of damage to the blood vessels of the retina at the back of the eye. The chronic occlusion of blood vessels that supply oxygen and nutrient to the retina and subsequent rupture and leakage of the blood vessels can trigger the progression of the disease. In the advanced stage of proliferative DR, growth of weak and abnormal blood vessels, inflammation of the neurons and glial cells and recruitment and activation of inflammatory cells from the circulation can lead to severe scar tissue formation in the retina and permanent vision loss in DR. There are currently no treatment options that can prevent the severe vision loss and blindness in people living with diabetes.
OCX063 for Diabetic Retinopathy
In a predictive rat model of DR, we have demonstrated that OCX063 can reduce the leakage and lesion of blood vessels and prevent the activation and recruitment of inflammatory cells in the retina, when administered at the onset of diabetes or after the disease is established.
*Adhesion of inflammatory cells in retinal circulation by fluorescence staining
Age-Related Macular Degeneration
Age-related macular degeneration (AMD) is the leading cause of blindness in the aging population in developed countries and is the third largest cause of visual impairment in the world.
AMD is a degenerative eye disease that affects the central area of the retina (macula) at the back of the eye, resulting in distortion or loss of vision in the middle of the visual field. The hallmark of early AMD is the presence drusen, seen as small deposits containing lipid and protein that can elicit local inflammation, underneath the pigmented layer of the retina. Here, the retinal pigment epithelium (RPE) plays a crucial role in the maintenance of visual function.
In the advanced stages of AMD, the widespread damage and loss of RPE (geographic atrophy) and subsequent degeneration of photoreceptors can cause a slow and gradual decline in central vision in dry AMD. There is currently no effective treatment for geographic atrophy in dry AMD. In contrast, wet AMD is characterised by the growth of abnormal blood vessels in the choroid (choroidal neovascularisation) at the back of the retina, which ultimately lead to leakage of blood and fluid into the space between the photoreceptor and RPE and rapid and severe loss of central vision. While treatment of wet AMD has been revolutionised by the use of anti-vascular endothelial growth factors, which has been shown to slow the progression of the disease, patients continue to loss their vision over time as a consequence of formation of scar tissue in the macula.
OCX063 for Age-Related Macular Degeneration
In the mouse model of laser-induced choroidal neovascularisation (CNV), which is the most robust and commonly used model for the study of wet AMD, we have demonstrated that OCX063 can prevent and reduce the size and leakage of the CNV lesions and fibrotic tissue content in the CNV lesions, when administered at the onset of disease or after lesions are established. The improvement of these pathological features by OCX063 was accompanied by changes of diverse genes responsible for angiogenesis, inflammation and fibrosis, known to contribute to the disease progression.
*Measurement of vascular leakage by fluorescein angiography.