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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/αVEGF bi-specific
Tie2 Agonistic Antibody
Diabetic Macular Edema (ASPIRE)
Diabetic Macular Edema (BEHOLD)
Retinal Vascular Diseases
Retinal Vascular Diseases
UBX1325 (Phase 2b)
Phase 2b
UBX1325 (Phase 2)
Phase 2
UBB2048
Lead Optimization
UBX2050
Lead Optimization
Neurology
Neurology
α-Klotho
Cognitive Disorders
UBX2089
IND-Enabling

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. The small molecule targets Bcl-xL, a protein that senescent cells rely on for survival. UBX1325 demonstrated a statistically significant and clinically meaningful improvement in mean Best Corrected Visual Acuity (BCVA) through 48 weeks compared to sham treatment in the Phase 2 BEHOLD study in patients with DME. A Phase 2b study (ASPIRE) is currently enrolling patients with DME and will evaluate UBX1325 head-to-head against aflibercept.

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.

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.

 

MoA animation by Visual Science, 2023

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). 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 retinal disease.

 

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. In addition, the leading anti-VEGF therapeutic requires 3-5 monthly loading doses followed by every 8-week dosing, imposing a significant treatment burden on patients.

CLINICAL TRIALS

UNITY is currently conducting the following clinical studies:
  • Active (recruiting): ASPIRE Phase 2b study evaluating the safety and efficacy of multiple doses of UBX1325 in patients with diabetic macular edema (NCT06011798)
  • Completed: BEHOLD Phase 2 study evaluating the safety and efficacy of UBX1325 in patients with diabetic macular edema (NCT04857996)
  • Completed: 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.