Unity reveals data from Phase 1 SAD study of UBX1325

Unity Biotechnology Inc. today announced 24-week data from its Phase 1 single ascending dose (SAD) safety study of UBX1325 in patients with advanced disease from diabetic macular edema (DME) or wet age-related macular degeneration (AMD).

A majority of patients with DME across all doses had rapid improvements in vision, and patients in the higher dose cohorts showed a mean gain of 9.5 ETDRS letters in best-corrected visual acuity (BCVA) at 24 weeks following a single injection of UBX1325.

A majority of wet AMD patients treated with UBX1325 showed rapid gains in visual acuity, which were maintained through 12 weeks. In most patients, central subfield thickness (CST) remained stable through the study period.

According to the company, the study enrolled a total of 19 patients with advanced DME (n=8) and wet AMD (n=11) for whom anti-VEGF therapy was no longer considered beneficial. UBX1325 was well-tolerated at all doses tested (through 10 mcg) with no dose-limiting toxicities and no reported incidence of inflammation.

The Phase 1 data show rapid improvements in visual acuity as measured by BCVA in patients with DME, with the majority of patients demonstrating sustained responses through 24 weeks:

• Across all DME patients enrolled (n=8), there was an improvement in visual acuity in 6 of 8 patients at 12 weeks, and in 5 of 8 patients at 24 weeks
• In the higher dose cohorts (5, 10 mcg), patients had a mean improvement of 9.5 ETDRS letters from baseline at 24 weeks
• Amongst all DME patients, 62.5% gained 5 or more letters at 24 weeks, and 50% gained 10 or more letters also at 24 weeks
• In the majority of patients with DME, CST remained stable through 24 weeks

“A 10 letter gain in DME patients, maintained through six months, is an impressive outcome, and is particularly noteworthy considering that it was achieved with a single injection,” Arshad Khanani, MD, MA, managing partner of Sierra Eye Associates, said in a statement. “Hard-to-treat patients require as many as 10 injections in the first year of treatment to see full benefits from currently available anti-VEGF therapies. A treatment that reduces the frequency of injections while showing meaningful and sustained improvements in BCVA would be of huge value for patients and physicians.”

The Phase 1 study included 11 wet AMD patients (4 in the SAD cohort, and an additional 7 in an expansion cohort). A majority of patients showed rapid improvements in visual acuity:

• Across all evaluable patients with wet AMD enrolled (10 of 11), there was an improvement in visual acuity in 7 of 10 patients at 8 weeks, and in 5 of 10 patients at 12 weeks
• 2 of 3 patients in the SAD cohort maintained their visual acuity gain through 24 weeks
• Within the ten evaluable patients with wet AMD, CST remained stable through 12 weeks; this trend was also observed in the three evaluable patients with wet AMD at 24 weeks, and 2 of those 3 patients showed resolution of most subretinal fluid

“Patients with wet AMD will lose vision without treatment and have a worse prognosis than patients with DME, which is why the letter gain seen in the AMD cohort is so meaningful,” Robert Bhisitkul, MD, PhD, professor of ophthalmology and director of the Retina Fellowship at University of California, San Francisco, said in a statement. “The efficacy that we are seeing in AMD patients provides a convincing rationale for advancing this program into additional clinical studies.”

Anirvan Ghosh, PhD, Unity’s CEO, noted that the study has now followed advanced DME and AMD patients for 24 weeks, and see clear evidence of rapid and sustained responses from a single injection of UBX1325.

“The improvements in vision and retinal structure suggest that this new mechanism of action – the selective elimination of senescent cells in diseased retinal tissue – has the potential for disease-modifying effect in a large proportion of patients struggling to manage their disease,” Ghosh said.

According to the company, its Phase 2 study of UBX1325 in DME is underway, with 12-week safety and efficacy data anticipated in the first half of 2022. A Phase 2 study in wet AMD is planned for the first half of 2022, with 12-week data expected in the second half of the year.