Over the arc of life, our cells burn nutrients and oxygen for energy to fulfill specialized functions such as transmitting sensorial information, transporting blood, and defending us from cancer or invading organisms. In the process, cells are exposed to biological and environmental stressors that ultimately damage the cell. A common complication of this cellular damage is called cellular senescence.
Senescent cells can secrete large quantities of harmful proteins, which cause inflammation, dysfunction, and tissue degradation, along with growth factors that alter the tissue microenvironment. Senescent cells are a salient feature of several age-related diseases.
UNITY is at the forefront of developing a new class of therapeutics intended to selectively eliminate or modulate senescent cells to halt, slow, or reverse age-related disease and restore aging or damaged tissue to a more functionally healthy state. We believe this therapeutic approach has the potential to address the root cause of many diseases of aging, such as retinopathies, neurodegenerative disorders, fibrosis, and cancer.
Increased senescent cell burden in ocular tissues is associated with ophthalmological disorders such as age-related macular degeneration (AMD) and diabetic macular edema (DME). We believe that therapeutic elimination of senescent cells may remove a significant source of disease-inducing factors in the eye, restore vasculature to a healthier state, and improve vision in patients with DME or AMD.
UBX1325 is a potent Bcl-xL inhibitor that has been demonstrated to selectively eliminate senescent cells in vitro and to inhibit retinal neovascularization, reduce vascular leakage, and improve retinal function in preclinical disease models. In a Phase 2 proof-of-concept study (BEHOLD) in patients with DME, a single injection of UBX1325 led to a statistically significant and clinically relevant improvement in mean Best Corrected Visual Acuity (BCVA) through 24 weeks compared to sham treatment. In addition, a Phase 2 study (ENVISION) of UBX1325 in patients with wet AMD is currently ongoing with 16-week safety and efficacy results expected in the first quarter of 2023.
The Tie2/angiopoietin signaling axis is critical to the maintenance of normal vascular homeostasis in ocular tissues and becomes dysregulated in age-related eye diseases. The imbalanced overexpression of angiopoietin-2 leads to Tie2 inhibition, a loss of vascular integrity, and pathological neovascularization. We believe that therapeutic re-activation of Tie2 signaling will restore ocular vasculature to a healthier state and improve vision in patients with DME or AMD.
UBX2050 is an investigational fully human Tie2-activating monoclonal antibody that has been shown to restore Tie2 function independently of angiopoietin-2 binding, inhibit choroidal neovascularization, and restore healthy vasculature in preclinical disease models.
Human and mouse genetic evidence has implicated α-Klotho as being essential for normal cognitive function. Therapeutic administration of α-Klotho may both enhance cognition acutely and delay, halt, or reverse the neurodegenerative disease process chronically.
We have observed therapeutic activity of recombinant α-Klotho (UBX2089) in multiple preclinical rodent models of neurological disease, as well as in non-human primates. Activity of UBX2089 continues to be explored in preclinical animal models with the intent of advancement to clinical studies.