Unity Biotechnology Announces Topline Results from the ASPIRE Phase 2b Study in DME

Unity Biotechnology announced topline results from the phase 2b ASPIRE clinical trial of intravitreal UBX1325 in patients with diabetic macular edema (DME) who had poor vision despite prior anti-VEGF treatment. The study results include data from all patients through 24 weeks, and the majority of patients through 36 weeks. UBX1325 treatment led to visual acuity gains of over 5 letters from baseline at weeks 24 and 36, and achieved noninferiority to aflibercept at 9 out of 10 time points through 36 weeks, except for the average of weeks 20 and 24, where it achieved noninferiority at an 88% confidence interval (compared to a 90% threshold pre-specified as primary analysis endpoint).

UBX1325 is a novel BCL-xL inhibitor that is designed to eliminate senescent cells in diabetic retinal blood vessels, while leaving healthy ones intact. UBX1325 is administered via intravitreal injections that are standard procedure in clinical practice.

“We are excited that UBX1325 showed robust vision improvements in a difficult to treat patient population,” Anirvan Ghosh, PhD, chief executive officer of Unity, said in a company news release. “The results also suggest that UBX1325 may provide greater vision gains than standard of care in patients with moderately aggressive disease. We look forward to advancing UBX1325 to late-stage studies against aflibercept in DME patients with inadequate response to anti-VEGF therapies.”

Phase 2b ASPIRE topline results from all subjects through 24 weeks and the majority of subjects through 36 weeks:

• Noninferior visual gains in best-corrected visual acuity (BCVA) compared to leading anti-VEGF product
  • UBX1325-treated patients had a mean change in BCVA of +5.2 ETDRS letters from baseline to 24 weeks, representing a difference of +0.4 ETDRS letters compared to the aflibercept arm
  • UBX1325-treated patients had a mean change in BCVA of +5.5 ETDRS letters from baseline to 36 weeks, representing a difference of +0.2 ETDRS letters compared to the aflibercept arm
  • UBX1325 was noninferior to aflibercept at all time points through 36 weeks, except for the average of weeks 20 and 24
  • Patients on UBX1325 had an increase in Central Subfield Thickness (CST) at weeks 16 and 20, which resulted in supplemental anti-VEGF treatments in patients with significant CST gain
• Sub-groups with consistent and durable vision gains with UBX1325
  • UBX1325 generally outperformed aflibercept in patients who had moderate disease severity (baseline CST < 400 microns, representing ~60% of study patients) (pre-specified analysis)
  • Patients who switched from aflibercept as their anti-VEGF treatment prior to study enrollment to UBX1325 had the most consistent and durable vision gains (pre-specified analysis)
• Favorable safety and tolerability profile
  • UBX1325 continues to demonstrate a favorable safety and tolerability profile across multiple clinical studies to date
  • There have been no cases of intraocular inflammation, retinal artery occlusion, endophthalmitis or vasculitis across multiple studies

“Achieving durable improvements in visual acuity via an entirely new mechanism of action as seen in this study is remarkable and would be invaluable for patients receiving sub-optimal response from current treatment options,” said David S. Boyer, MD, partner at Retina Vitreous Associates Medical Group and adjunct clinical professor of ophthalmology at Keck School of Medicine of USC. “Currently, about half of all patients don’t get optimal results from standard of care treatment and end up cycling through various anti-VEGF-based treatments which do not provide additional vision benefit. UBX1325, if approved, could help patients break out of this burdensome cycle and would be a welcome treatment alternative for patients.”

Unity anticipates the complete 36-week data results of the remaining patients in the second quarter of 2025.