We are developing therapeutics that target senescence and adjacent biology with broad application across multiple indications with established endpoints and well-defined regulatory pathways to approval. Our initial focus is on delivering localized therapy in ophthalmologic and neurologic diseases.
UNITY’s most advanced drug candidate, UBX1325, is currently being evaluated for the treatment of age-related diseases of the eye – including diabetic macular edema, diabetic retinopathy, and age-related macular degeneration. The small molecule targets Bcl-xL, a protein that senescent cells rely on for survival. UBX1325 demonstrated a favorable safety profile and sustained improvements in visual acuity through 24 weeks in a Phase 1 study of patients with advanced vascular eye disease. The initial assessment of patients in this study did not reveal any dose limiting toxicities or treatment-emergent adverse events, supporting initiation of a Phase 2 proof-of-concept study (BEHOLD) in DME to evaluate the safety and efficacy of UBX1325. Twelve-week results from BEHOLD are expected by mid-year 2022. A Phase 2 study (ENVISION) in wet AMD is also recruiting patients with 16-week data expected in the fourth quarter of 2022. UBX1967 remains in the portfolio as a molecularly distinct backup to UBX1325.
UNITY is also advancing programs that target the Tie2 signaling pathway for therapeutic benefit. Tie2 pathway activity decreases with age and leads to the loss of vascular barrier integrity and diseased blood vessel formation in the eye. UNITY’s Tie2/VEGF bispecific molecule is designed to target two pathways believed to be core to disease progression in DME and AMD. A separate program directed at Tie2 activation is being explored in preclinical studies for multiple indications, including Diabetic Kidney Disease.
UNITY’s neurology programs aim to explore novel mechanisms for cognitive benefit, and UNITY licensed its α-Klotho program, UBX2089, to Jocasta Neuroscience for development and commercialization in cognitive dysfunction associated with neurological and psychiatric conditions.
According to the National Eye Institute, diabetic retinopathy is the most prominent complication of diabetes and the leading cause of blindness in working age individuals. NEI estimates that ~8 million Americans are afflicted by the eye disease and predicts the incidence will double over the next 15 years. In diabetic retinopathy, the small caliber blood vessels that feed the back of the eye (retina) degenerate and re-grow in an abnormal manner. These diseased vessels obstruct light and can leave scars in the retina. Diabetic macular edema is a common complication of diabetic retinopathy and the leading cause of blindness in adults with diabetes.
During the course of diabetes, cells that make up the small caliber blood vessels in the eye are more likely to become senescent. We believe these senescent vascular cells compromise the integrity of the blood vessel and release inflammatory factors that collectively compromise healthy vasculature. In DME, the damaged blood vessels leak into the retina, resulting in the accumulation of fluid in the macula – or the central part of the retina. Over time, the macula swells and may lead to severe vision loss.
One of the limitations of the current standard of care, anti-VEGF therapy, for vascular diseases of the retina is that they target both sick and healthy parts of the eye and hence can potentially impair normal remodeling of healthy vessels. Anti-VEGF agents, for example, block all blood vessel growth. Bcl-xL inhibition may be the key to a new class of neovascular treatments that provide a viable and much needed alternative to current treatment modalities.