Science
Addressing Tremendous Unmet Need for Patients with Ophthalmic Diseases
Developing an earlier intervention in diabetic retinopathy, helping to prevent or slow disease progression
Diabetic retinopathy is the most common diabetic eye disease and the leading cause of vision loss and blindness in American working age adults.
Caused when high blood sugar levels damage blood vessels in the retina, early symptoms include floaters, blurriness, fluctuating vision and difficulty perceiving colors. However, diabetic retinopathy is often uncovered during a dilated eye exam and may be found before the patient notices any vision problems.
With a lack of non-invasive treatment options available today for patients with nonproliferative diabetic retinopathy (NPDR), the current standard of care is active surveillance or “watch-and-wait” until a sight threatening complication arises or vision deteriorates further.
When complications arise or vision deteriorates, the patient must undergo injections of medication, usually anti-VEGF (anti vascular endothelial growth factor) directly into the back of their eye (intravitreal injection), or destructive laser procedures in order to help stop the growth of new blood vessels and decrease fluid buildup. Typically, these injections are required monthly for the rest of the patient’s life. Pan-retinal photocoagulation (PRP) laser is well known to affect peripheral vision and night driving.
Diabetic Retinopathy Preferred Practice Pattern®. American Academy of Ophthalmology, 2019. http://dx.doi.org/10.1016/j.ophtha.2019.09.025
American Society of Retina Specialists Clinical Practice Guidelines: Management of Nonproliferative and Proliferative Diabetic Retinopathy Without Diabetic Macular Edema, 2020. https://doi.org/10.1177/2474126419893829
Cases of diabetic retinopathy in the U.S. projected to almost double by 2030
With cases of diabetic retinopathy in the U.S. projected to almost double by 2030, OcuTerra aims to change the course of treatment and ultimately preserve vision.
Its topical compound, OTT166, has been specifically designed to be administered as an eye drop by the patient at home at the earliest signs of diabetic retinopathy. By enabling earlier non-invasive treatment, OcuTerra’s goal is to prevent progression, thereby delaying or completely eliminating the need for intravitreal injections and/or destructive laser procedures.
OTT166 is a novel, patented, potent and selective small molecule RGD-binding integrin inhibitor developed to be administered in eye drop form by the patient at home.
It has been purpose engineered to have an optimum balance of physiochemical properties to allow it to distribute to the retina in high concentrations after topical administration. OTT166 is currently being studied in the Phase 2 DR:EAM (Diabetic Retinopathy: Early Active Management) clinical trial, evaluating the safety and efficacy of this candidate in patients with diabetic retinopathy as well as identifying an optimum dosing regimen for Phase 3.
OTT166 Inhibits Integrins Central to Diabetic Retinal Disease
OTT166 selectively inhibits key RGD integrin subtypes αvβ1, αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and α8β1 to regulate cellular responses to VEGF and other growth factors known to produce angiogenesis, vascular leakage (macula edema), fibrosis and inflammation that contribute to development and progression of diabetic retinopathy and other ocular diseases.
In DR, growth factors and other proteins bind to receptors resulting in new blood vessel growth and vascular leakage. Integrins, which play a role in the disease, are transmembrane receptors that mediate cellular communication and facilitate signaling by growth factors and other proteins.
OcuTerra is developing an investigational topical therapy, OTT166, as a potent selective RGD-binding integrin inhibitor that disrupts intracellular signaling induced by growth factor binding. OTT166 is designed to have the physiochemical properties to non-invasively reach the retina.
By targeting RGD-binding integrins including αvβ3, OTT166 is designed to regulate cellular responses to VEGF and other growth factors to prevent or slow DR progression.
Integrin inhibition – promising new target for retinal disease
Named for their function as ‘integrators’ of cell surface and extracellular matrix, integrins are transmembrane receptors that are the bridges for cell-cell and cell-extracellular matrix interactions. They modulate the intricate molecular pathways and regulate the underlying pathological mechanisms in complex multifactorial retinal disorders like diabetic retinopathy, diabetic macular edema (DME) and age-related macular degeneration (AMD).