ASRS 2022 – Phase 1 data from UBX1325

Prashant Tailor, MD
Mayo Clinic

Dr. Raj Maturi, MD presented on UBX1325, A Novel Senolytic Therapy for Treatment Experienced Patients With Chronic DME or Wet AMD: 24-Week Results of a Phase 1 Study. First, Dr. Maturi discussed how cell stress leads to increased senescent cells which induce a host of inflammatory cytokines subsequently leading to fibrosis and other adverse effects. The idea behind UBX1325 was to develop a specific therapy to remove senescent cells thereby removing these harmful cytokines. UBX1325 is a novel irreversible inhibitor of BclxL.

In this phase 1, prospective open label study, the goal was to assess the safety, tolerability, and disease relevant activity of a single intravitreal injection of UBX1325 in experienced subjects with chronic DME or wet AMD. There were 4 cohorts at 0.5, 1, 5, and 10 micrograms respectively. Subjects received one dose of UBX1325 intravitreally and were followed for 24 weeks.

In terms of the safety and tolerability endpoints, UBX1325 was well tolerated and did not show dose limiting toxicities or evidence of inflammation, infection, hemorrhage, and/or IOP increases. DME subjects with higher doses of UBX1325 experienced rapid increases of BCVA within 2 weeks and roughly half of subjects maintained 10 letter improvement at 24 weeks. CST remained stable through 24 weeks in most subjects with DME. Similarly, Wet AMD patients experienced a rapid gain in BCVA within 2 weeks; however, more patients required rescue therapy at 24 weeks.

During the Q&A session, the audience asked Dr. Maturi about what other applications senolytic therapy and systemic complications. It was discussed how the researchers expected systemic exposure to be low given the prodrug delivery and fast clearance in the eye.