UNITY Biotechnology, Inc. Announces New Publication In Nature Medicine Supports Therapeutic Potential Of Senolytics To Provide Long-lasting, Disease-Modifying Intervention In Vision Loss

Author: Benzinga Newsdesk | February 06, 2024 09:04am

UNITY Biotechnology, Inc. ("UNITY") (NASDAQ:UBX), a biotechnology company developing therapeutics to slow, halt or reverse diseases of aging, today announced new research published in the peer-reviewed journal Nature Medicine that supports the clearance of senescent cells in the retina as a therapeutic approach that can lead to long-term improvements in vision in patients with diabetic macular edema (DME). Sustained hyperglycemia from diabetes induces cellular senescence which damages the retina, including the delicate vasculature in the eye. This can lead to fluid accumulation and retinal thickening – a key feature of DME. The study shows that the therapeutic clearance of senescent cells can potentially remove an underlying source of pathogenesis and thus allow healthy cells to regenerate and remodel retinal vasculature, ultimately leading to long-term disease modification.

 

Multiple studies have demonstrated that cells enter a state of senescence, in which they remain viable and metabolically active in the body, yet generate various inflammatory factors and metalloproteases. These senescent cells can modify the surrounding environment and contribute to different cellular dysfunction and tissue degeneration. A team of scientists at University of Montreal and UNITY Biotechnology revealed that cellular senescent pathways are triggered in the diabetic retina and are specifically activated in endothelial cells. They demonstrated that these senescent cells contribute to loss of barrier function, which can cause leaky blood vessels.

Researchers showed that senolysis through BCL-xL inhibition improved retinal barrier function in diabetic mice, modifying the retinal microenvironment and reestablishing tissue homeostasis. In addition, in clinical trials BCL-xL inhibition led to improvements in visual acuity and retinal structure stabilization in patients with advanced disease.

"This research provides compelling mechanistic evidence of the therapeutic approach of eliminating senescent cells to reduce diabetes-induced retinal vascular leakage and preserve retinal function," Anirvan Ghosh, Ph.D., chief executive officer of UNITY and an author of the paper. "As senescent cell burden is observed in many other diseases, this study highlights the potential benefit of senolytic drugs for various age-related and metabolic diseases."

The BCL-xL inhibitor UBX1325 has been evaluated in a Phase 2 study as well, as previously announced, which demonstrated that a single injection led to statistically significant and clinically meaningful improvements in visual acuity through 48 weeks in patients with DME, while reducing anti-VEGF treatment burden. UNITY is actively enrolling patients for a Phase 2b clinical trial where UBX1325 is being evaluated head-to-head versus aflibercept, with 16-week results expected in Q4 2024.

"Most therapeutic options available and in development for DME target the VEGF pathway. As a BCL-xL inhibitor, the senolytic UBX1325 targets an alternative mechanism and holds the potential to not only address the limitations of but also compliment anti-VEGF agents," said Przemyslaw (Mike) Sapieha, Ph.D., chief scientist at UNITY and the lead author of the paper. "A new long-lasting and disease-modifying therapy for DME would be transformative for patients. This research further supports the potential for senolytic medicines to address the significant unmet need with current standard of care."

About UBX1325

UBX1325 is an investigational compound being studied in retinal diseases, including DME and wet AMD, and is not approved for any use in any country. UBX1325 is a potent small molecule inhibitor of BCL-xL, a member of the BCL-2 family of apoptosis regulating proteins. UBX1325 is designed to inhibit the function of proteins that senescent cells rely on for survival. The Phase 2 BEHOLD study in patients with DME demonstrated that a single injection of UBX1325 resulted in a statistically significant and clinically meaningful improvement in mean Best Corrected Visual Acuity (BCVA) through 48 weeks compared to sham treatment. In preclinical studies, UNITY has demonstrated that targeting Bcl-xL with UBX1325 preferentially eliminated senescent cells from diseased tissue while sparing cells in healthy tissue. UNITY's goal with UBX1325 is to transformationally improve real-world outcomes for patients with retinal disease.

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