AnaptysBio, Inc. announced positive top-line data from a Phase 1 trial of ANB032, its investigational wholly owned anti-BTLA agonist antibody. Top-line data demonstrated favorable safety, tolerability, and a rapid and sustained pharmacokinetic and pharmacodynamic profile that supports advancement of ANB032 into subsequent patient trials. AnaptysBio has a strategic portfolio review ongoing while continuing to execute on the development of its three wholly owned clinical stage antibody programs: Imsidolimab (anti-IL-36R Ab) top-line data from the GEMINI-1 Phase 3 trial in GPP is anticipated in the fourth quarter of 2023; Imsidolimab top-line data from the HARP Phase 2 trial in moderate-to-severe hidradenitis suppurativa is anticipated in the third quarter of 2022; Rosnilimab (anti-PD-1 agonist Ab) top-line data from the AZURE Phase 2 trial in moderate-to-severe alopecia areata is anticipated in the first half of 2023; ANB032 (anti-BTLA agonist Ab) IND filing of a Phase 2 clinical trial is anticipated in the second half of 2022. A total of 96 subjects were enrolled in the randomized, double-blind, placebo-controlled healthy volunteer Phase 1 trial, where single ascending dose (SAD) cohorts received subcutaneous or intravenous single doses of ANB032 or placebo, while multiple ascending dose (MAD) cohorts received four weekly subcutaneous doses of ANB032 or placebo.

ANB032 was generally well-tolerated, no dose limiting toxicities were observed and there were no discontinuations due to adverse events, other than one patient quarantined for potential COVID infection.  No serious adverse events (SAEs) were reported.  Most adverse events were considered to be mild-to-moderate, of short duration, resolved without sequelae and occurred sporadically in a dose-independent manner.   Three severe adverse events (2 blood creatine phosphokinase (CPK) increase and 1 aspartate aminotransferase (AST) increase), none of which were treatment-related, were reported in two subjects in the lowest dose MAD cohort.

Three subjects had mild-to-moderate single injection site reactions (ecchymosis; erythema; and pain) of short duration. Pharmacokinetic analyses demonstrated a favorable profile for ANB032 including an approximate two-week half-life for subcutaneous and intravenous routes of administration. Full BTLA receptor occupancy was observed rapidly within hours and was maintained for greater than 30 days following IV or subcutaneous ANB032 dosing.

ANB032 pharmacodynamic activity resulted in reduction of cell surface BTLA expression on T cells and B cells following dosing. A portion of the cell surface BTLA was shed from the cells as soluble BTLA (sBTLA), while the residual approximately 60% of baseline BTLA on T cells and B cells remained occupied by ANB032. The duration of reduced BTLA expression correlated with receptor occupancy in a dose-dependent manner and was maintained for greater than 30 days following IV or subcutaneous ANB032 dosing.