88 ANB032, a novel BTLA agonist monoclonal antibody, inhibits T cell proliferation, reduces inflammatory cytokines, and down modulates BTLA expression on circulating T and B cells

ANB032, a BTLA agonist antibody, has potential to modulate the pathogenic inflammatory response with broad applicability to inflammatory diseases where the BTLA pathway is dysregulated. In preclinical studies, ANB032 inhibited activated T cell proliferation, reduced inflammatory cytokine secretion (Th1, Th2, Th17, Th22) and modulated dendritic cell function, including inducing T regs. We report a Phase 1 double-blind, placebo-controlled, single ascending dose (SAD) and multiple ascending dose (MAD) study of ANB032 in 96 healthy subjects. SAD and MAD consisted of 8 subjects each (6 ANB032, 2 placebo via intravenous or subcutaneous injection). SAD included 9 cohorts while MAD included 3 cohorts with each cohort dosed with ANB032 or placebo weekly for 4 weeks. Results were similar for both cohorts. ANB032 was well-tolerated with no dose limiting toxicities, no discontinuations due to adverse events (AEs) (except for one subject with potential COVID infection), or SAEs. Most AEs were mild-to-moderate, of short duration, resolved without sequelae, occurred sporadically, and were dose-independent. PK profile was favorable, including a 2-week half-life. Full BTLA receptor occupancy (RO) occurred within hours and was maintained for >30 days after a single dose. Moderate reduction (∼50%) of cell surface BTLA expression on T and B cells was observed. The duration of reduced BTLA expression dose-dependently correlated with RO and was maintained for >30 days after a single dose. This study demonstrated robust PK, favorable safety, and target engagement in humans. A global Phase 2b trial in AD began May 2023 with results expected EOY 2024.