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 is pursuing multiple approaches to target novel biology in eye diseases. UBX1325, a potent Bcl-xL inhibitor, 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 proteins that senescent cells rely on for survival. A Phase 1 study is exploring the safety and tolerability of UBX1325 in patients with diabetic macular edema or age-related macular degeneration. 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 2a proof-of-concept study in DME to evaluate the safety and efficacy of UBX1325. Initial data from this Phase 2a study is expected in the first half of 2022. UBX1967 remains in the portfolio as a molecularly distinct backup to UBX1325.
UNITY is also developing a novel antibody with a unique mechanism of action that activates the Tie2 pathway in age-related eye diseases. 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 activator, UBX2050, aims to restore healthy vasculature and function in diabetic macular edema, independent of Bcl-xL inhibition.
UNITY’s neurology programs build upon our foundational cellular senescence research platform to target core features of neurodegenerative diseases and cognitive disorders. These programs will focus on developing senolytic therapies for neurological diseases and complement the on-going exploration of novel mechanisms for cognitive benefit, including α-Klotho, UBX2089.
Our other research programs will also explore therapeutic modalities beyond small molecule approaches to significantly expand the target space for modulating senescent cell biology implicated as drivers of age-related diseases.
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.