When Headlines Miss the Science: Inside Unity’s Senolytic Breakthrough

While offering one of the strongest validations to date of senescence as a therapeutic target.

When Unity Biotechnology announced results from their two Phase 2 trials — BEHOLD (phase 2) and ASPIRE (phase 2b) — the reaction was swift: headlines declared failure. But only one of those trials — ASPIRE — missed its primary endpoint. BEHOLD, a placebo-controlled study, met its pre-specified endpoint. While one technically missed its mark, both trials tell a compelling scientific story and delivered some of the most promising clinical data in the senolytic field to date.

Why two trials? BEHOLD and ASPIRE were designed to answer two distinct questions. BEHOLD asked: Does UBX-1325 work on its own?

ASPIRE asked: Can it outperform standard of care? Running both in parallel made strategic sense — isolating efficacy in one trial, while testing competitive positioning in the other.

And the results were revealing. BEHOLD confirmed UBX-1325’s standalone efficacy, with long-lasting improvements from a single injection. ASPIRE, though missing its primary endpoint, hinted at something even more profound: that over time, UBX-1325 might actually outperform standard of care, especially in patients who are in earlier stages of disease and have milder disease. Had ASPIRE run longer, it would likely have reached statistical significance. But in biotech, trial length is often a function of financial reality.

In an extended interview with Unity’s Chief Scientist, Mike Sapieha, PhD, we explored what the data actually shows, and why this may be a turning point for senescence-targeting therapeutics.

Understanding the Disease and the Mechanism

Unity’s drug candidate, UBX-1325, was developed for Diabetic Macular Edema (DME), the leading cause of vision loss in people with diabetes. The culprit? Senescent cells: damaged, non-dividing cells that linger in tissues and emit inflammatory signals, causing swelling and tissue dysfunction.

Whereas current treatments like Eylea suppress Vascular Endothelial Growth Factor to reduce retinal fluid, UBX-1325 takes a fundamentally different approach: eliminating the root cause (senescent cells) via BCL-xL inhibition, a member of the BCL-2 protein family that enables these pathiological senescent cells to avoid undergoing apoptosis.

"For the first time, we have a non-VEGF or non-steroid-based mechanism that showed clinically meaningful gains in visual acuity similar to VEGF in a controlled trial— at nearly all timepoints except one." – Mike Sapieha, PhD

To understand why this matters, we can look at preclinical models. In a mouse model of diabetes, BCL-xL ...