June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
UBX1325, A Novel Senolytic Treatment for Patients with Advanced DME or wet AMD: 24-Week Results of a Phase 1 Study
Author Affiliations & Notes
  • Robert Bhisitkul
    University of California San Francisco, San Francisco, California, United States
  • Sharon Klier
    UNITY Biotechnology, South San Francisco, California, United States
  • Pamela Tsuruda
    UNITY Biotechnology, South San Francisco, California, United States
  • Ben Xie
    UNITY Biotechnology, South San Francisco, California, United States
  • Lauren Masaki
    UNITY Biotechnology, South San Francisco, California, United States
  • Jessica Bautista
    UNITY Biotechnology, South San Francisco, California, United States
  • Akbar Khan
    UNITY Biotechnology, South San Francisco, California, United States
  • Jamie Dananberg
    UNITY Biotechnology, South San Francisco, California, United States
  • Footnotes
    Commercial Relationships   Robert Bhisitkul UNITY Biotechnology, Code C (Consultant/Contractor); Sharon Klier UNITY Biotechnology, Code E (Employment); Pamela Tsuruda UNITY Biotechnology, Code E (Employment); Ben Xie UNITY Biotechnology, Code E (Employment); Lauren Masaki UNITY Biotechnology, Code E (Employment); Jessica Bautista UNITY Biotechnology, Code E (Employment); Akbar Khan UNITY Biotechnology, Code C (Consultant/Contractor); Jamie Dananberg UNITY Biotechnology, Code E (Employment)
  • Footnotes
    Support  UNITY Biotechnology
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4287. doi:
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    • Get Citation

      Robert Bhisitkul, Sharon Klier, Pamela Tsuruda, Ben Xie, Lauren Masaki, Jessica Bautista, Akbar Khan, Jamie Dananberg; UBX1325, A Novel Senolytic Treatment for Patients with Advanced DME or wet AMD: 24-Week Results of a Phase 1 Study. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4287.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Cellular senescence is implicated in retinal microvascular pathology that drives disease in DME and wet AMD. UBX1325, a novel small molecule Bcl-xL inhibitor, is a potent senolytic agent. This prospective study assessed the safety, tolerability, and disease-relevant activity of a single intravitreal (IVT) injection of UBX1325 in patients with advanced DME and wet AMD.

Methods : A phase 1, open-label, single ascending dose study (www.clinicaltrials.gov NCT04537884) was conducted in 4 cohorts at 0.5, 1, 5, and 10 μg, respectively. 12 patients, 2 with DME and 1 with wet AMD in each cohort, were enrolled. 7 additional patients with wet AMD were enrolled in the 10 µg cohort. Patients with DME or wet AMD meeting best corrected visual acuity (BCVA) criteria, no anti-VEGF for ≥90 days prior to Day 1, and with macular fluid or, for AMD, subretinal (SR) and/or intraretinal (IR) fluid were eligible to be enrolled. Patients received UBX1325 IVT once and followed through 24 weeks. Safety, change from baseline in BCVA and CST through study end were analyzed.

Results : UBX1325 was well tolerated with a favorable safety profile throughout. No dose-limiting toxicities or evidence of inflammation, infection, hemorrhage, or increase in intraocular pressure were observed.

Amongst 8 patients with DME, BCVA improved in 6 at Week 12, and in 5 at Week 24. At Week 24, 62.5% of patients gained ≥5 letters and 50% gained ≥10 letters. CST remained stable through 24 weeks in most patients with DME. Through 24 weeks, 62.5% of patients did not meet rescue criteria (≥75 µm CST increase from trough or ≥10 ETDRS letters decrease from peak) after UBX1325.

Amongst 10 evaluable patients (of 11) with wet AMD, visual acuity was improved in 7 at 4 weeks and in 5 at Week 12 and CST remained stable through 12 weeks. 80% of patients did not meet rescue criteria through 12 weeks. Reduction in SR and IR fluid was also observed. Additional 24-week data will be available for presentation.

Conclusions : A single IVT injection of UBX1325 up to 10 μg was safe and well tolerated in patients with advanced DME or wet AMD, through 24 weeks. Disease-relevant improvements in BCVA, CST, and IR and SR fluid, were observed in treated subjects. These data support further development of UBX1325, a novel senolytic small molecule, for DME and wet AMD.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

 

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