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CLINICAL DEVELOPMENT STRATEGY

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.

PIPELINE

Mechanism
Indication
Research
Lead Optimization
IND-Enabling
Phase 1
Phase 2
Phase 3
Ophthalmology
Ophthalmology
Bcl-xL Inhibition
Tie2 Activation
Tie2/VEGF bi-specific
Diabetic Macular Edema, Diabetic Retinopathy, Age-Related Macular Degeneration
UBX1325
Phase 2
UBX1967
IND-Enabling
UBX2050
IND-Enabling
Lead Optimization
Neurology
Neurology
α-Klotho
Senolytics
Cognitive Disorders
Neurodegenerative Disorders
UBX2089
IND-Enabling
Undisclosed
Lead Optimization
Growth Areas
Growth Areas
Multiple Mechanisms
Multiple Indications
Undisclosed
Lead Optimization

LEAD PRODUCT CANDIDATES

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.

 

UBX1325

Overview

UBX1325, a potent Bcl-xL inhibitor, is in clinical development for the treatment of age-related diseases of the eye, including diabetic macular edema (DME), age-related macular degeneration (AMD), and diabetic retinopathy (DR). UBX1325 is designed to selectively eliminate the senescent cells accumulating in diseased blood vessels of the eye. This novel approach to eye disease has the potential to target diseased vasculature while leaving healthy blood vessels intact, reestablish barrier function in the eye, and reverse progression of disease. UNITY’s goal with UBX1325 is to transformationally improve real-world outcomes for patients with DR, DME, and AMD.

 

Retinal Bcl-xL inhibition

UBX1325 is the first senolytic approach intended to target senescent cells and selectively eliminate these cells in and around diseased vasculature in the eye, while leaving healthy blood vessels intact. UBX1325 is a novel senolytic small molecule inhibitor of Bcl-xL, a member of the Bcl-2 family of apoptosis regulatory proteins that is highly expressed in pathological blood vessels in the retina. Inhibition of Bcl-xL promotes apoptosis of diseased senescent cells, which accumulate in the retina, promoting inflammation and compromising vascular integrity. In preclinical research published in Cell Metabolism, a single dose of UNITY’s Bcl-xL small molecule inhibitor led to selective elimination of senescent cells in diseased vasculature, while enabling functional, healthy blood vessels to reorganize and regenerate.

 

NEW APPROACH FOR DIABETIC EYE DISEASE

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.

CLINICAL TRIALS

UNITY is currently conducting the following clinical studies:
  • Completed: Phase 1 study evaluating a single dose of UBX1325 in patients with diabetic macular edema or age-related macular degeneration (NCT04537884)
  • Enrollment Completed: BEHOLD Phase 2 study evaluating the safety and efficacy of UBX1325 in patients with diabetic macular edema (NCT04857996)
  • Recruiting: ENVISION Phase 2 study evaluating the safety and efficacy of UBX1325 in patients with wet age-related macular degeneration (NCT05275205)
For patients or physicians interested in learning more about the studies, please visit clinicaltrials.gov.