ANB032 — Overview

ANB032 is a novel, non-depleting antibody that binds to the BTLA checkpoint receptor and inhibits activated T cell proliferation, reduces inflammatory cytokine secretion and modulates dendritic cell (DC) function, including inducing Tregs, both in inflamed tissue and the periphery

ANB032 has potential to treat a wide range of systemic inflammatory diseases

ANB032: IgG4 antibody (non-depleting)

  • Binds to BTLA on epitope proximal to immune cell
  • Fc receptor binding profile contributes to differentiated potency
  • Non-blocking of HVEM engagement with optimized antigen binding affinity

ANB032’s agonist signal modulates immune cells

  • Inhibits activated T cell proliferation
  • Reduces inflammatory cytokine secretion
  • Modulates DC function, including inducing Tregs

BTLA is key node of immune regulation

  • B and T lymphocyte attenuator (BTLA) is a potent modulator of T cells, B cells and dendritic cells (DC)
  • Expressed only on immune cells and preferentially on activated immune cells
  • Dysregulation of BTLA pathway accelerates onset and exacerbates disease

ANB032’s optimized Fc receptor engagement significantly enhances BTLA agonism

Jurkat BTLA SHP2 Recruitment Assay methodology: BTLA and SHP2 are fused with complementary enzyme fragments, when SHP2 is recruited to activated phosphorylated BTLA, the enzyme donor and enzyme acceptor form active β-gal that is detected by chemiluminescence.

ANB032 demonstrated favorable safety and tolerability with rapid and sustained PK/PD activity

96 healthy volunteers in SAD and MAD cohorts in Phase 1 study

  • Favorable ~2-week half-life with IV and SQ dosing
  • Full receptor occupancy (RO) within hours and maintained for >30 days

Rapid and sustained target engagement on both T and B cells

  • Duration of reduced BTLA expression persisted in dose-dependent manner

Well-tolerated with no dose limiting tox

  • No SAEs
  • Most AEs mild-to-moderate, short duration, dose independent and resolved without sequelae
  • No evidence of infection risk or cancer risk to date