UNITY Biotechnology, Inc. announced the design for its Phase 2 study of UBX1325 in wet age-related macular degeneration (AMD) and anticipated milestones for 2022. UNITY expects to share 12-week safety and efficacy data from its ongoing Ph2 study of UBX1325 in DME in the first half of 2022, and to share initial data from the Ph2 study in wet AMD in the second half of 2022. UBX1325 Program: The protocol for the Phase 2 proof of concept study of UBX1325 in wet AMD has been submitted to the U.S. FDA and anticipate initiating that study in the first half of 2022.

The Phase 2 clinical trial is a multi-center, randomized, double-masked study designed to evaluate the safety, efficacy and durability of UBX1325. The study design includes a control arm using standard-of-care aflibercept in patients with neovascular AMD. Patients will be randomized to receive either two doses of UBX1325 10 mcg at week 0 and week 4, or aflibercept 2 mg every eight weeks.

Safety and efficacy will be assessed at 8, 16 and 24 weeks. The primary endpoint is improvement in visual acuity, as measured by change in BCVA from baseline. The study is expected to enroll 46 patients with wet AMD who have had at least three intravitreal injections of anti-VEGF therapy in the preceding six months and who have residual sub- or intra-retinal fluid.

Patients will have received their last anti-VEGF treatment approximately 4-8 weeks prior to screening, and all patients will be followed for approximately 24 weeks after dosing with either UBX1325 or aflibercept. Additional Pipeline Programs: UNITY continues to investigate new modalities around senescence-related mechanisms and other biology implicated as drivers of diseases of aging: Tie2-VEGF bispecific program: Tie2 is a receptor tyrosine kinase that is implicated in regulating barrier function in blood vessels of the eye, which are affected in several prevalent eye diseases. Tie2 is an important key regulator of the vascular endothelium in the eye and dysregulation of this pathway leads to loss of barrier integrity and healthy vasculature.

Preliminary studies suggest that cellular senescence in aging eyes may induce Ang-2 and therefore deactivate Tie2, leading ocular edema. The Tie2-VEGF bispecific has dual functionality on two validated targets for retinal diseases. In addition to direct activation of Tie2, the bispecific candidate is designed to neutralize VEGF-A and VEGF-B. UNITY anticipates that a Tie2 x VEGF bispecific clinical candidate will be selected and enter IND-enabling studies in 2022.

Believe that direct agonism of Tie2 may be superior to antagonism of Ang2 which relies on adequate levels of endogenous Ang1 to activate the Tie2 pathway. UBX2050 Tie2 antibody program:The investigational Tie2 antibody (UBX2050) may be an orthogonal approach to restoring barrier function and vascular function. UNITY is exploring a number of indications for UBX2050 and expects to nominate a Development Candidate in 2022.

UBX2089 -Klotho program: UNITY has licensed its a-Klotho (UBX2089) program to Jocasta Neuroscience for development and commercialization in cognitive dysfunction associated with neurological and psychiatric conditions (add link to press release). The a-Klotho protein has been implicated in human cognition and may provide benefits in age-related cognitive diseases, including Alzheimer's Disease. The licensing agreement included an upfront payment and provides for development and approval milestones, as well as sales-based royalties per indication.

UBX2089 is expected to enter IND-enabling studies in 2022. Discovery programs: UNITY continues to advance preclinical programs targeting new mechanisms of action for the treatment of age-related diseases, including both senolytic and non-senolytic mechanisms. Anticipated 2022 Milestones: 1H 2022 – UBX1325 complete safety and efficacy data through 24 weeks from the additional wet AMD cohort of the Phase 1 study (UBX1325-01 Study), 1H 2022 – UBX1325 12-week safety and efficacy data from the Phase 2a DME study (UBX1325-02 Study), 2H 2022 – UBX1325 24-week safety and efficacy data from the Phase 2a DME study (UBX1325-02 Study), 2H 2022 – UBX1325 16-week safety and efficacy data from the Phase 2 wet AMD study (UBX1325-03 Study), 2022 – Tie2 antibody (UBX2050), Tie2/VEGF bispecific and -Klotho (UBX2089) projected to enter IND-enabling studies.