NeuroMab™ Anti-HMGB1 BBB Shuttle Antibody(NRZP-1022-ZP4006)

Figure 1 Binding kinetics and specificity of human anti-HMG1 antibodies.

HMG1 capture ELISA binding curves of several human anti-HMG1 antibodies comparing capture of native nuclear, necrotic and activated HMG1 showed that S6 and to a lesser extent G4 bound to various forms with different affinities, while S16 did not.

Figure 2 HMG1 B-box epitope mapping study. HMG1 B-box peptide ELISA binding curves for several human anti-HMG1 antibodies are shown.

The curves indicate binding of S12, S16 and G4 to HMG1 peptide 91-169.

Figure 3 Human anti-HMG1 antibody inhibits HMG1-stimulated cytokine release from human PBMC

Representative dose-response curves are shown for naturally activated HMG1-stimulated IL-6 cytokine release inhibition of E11, S13, S16, S17, G4, G9, S6, RAGE-Fc and A-box fusion proteins.

Figure 4 Human anti-HMG1 antibody inhibits HMG1-stimulated cytokine release from human PBMCs.

Representative dose-response curves of recombinant HMG1-stimulated IL-1B, IL-6, and TNF-α release inhibitory activity against several human anti-HMG1 antibodies (G9, S14, G20, S2, S6, and S17) are shown.

Figure 5. Human anti-HMG1 antibody is protective in a mouse CLP model of sepsis.

Shown are representative survival curves of a mouse CLP model of sepsis comparing treatment with human anti-HMG1 antibody or human isotype control antibody (R3-47).

Figure 6. Human anti-HMG1 antibody is protective in a mouse CLP model of sepsis.

Shown are representative survival curves of a mouse CLP model of sepsis comparing treatment with human anti-HMG1 antibody or human isotype control antibody (R3-47).

Figure 7. Synergy between HMG1 and the TLR4 ligand LPS. Left panel) Treatment of human PBMCs with rHMG1 (black bars) stimulated the release of several cytokines (IL-6, MIP-1b, IL-8, and TNF), whereas cells treated with Triton-extracted HMG1 (white bars) did not Stimulate.

Human PBMCs treated with Triton-extracted HMGB1+LPS with anti-TLR4 antibodies or anti-HMG1 antibodies E11, S16, or G4 showed reduced IL-6 release to near background levels, whereas cells treated with isotype control antibodies (R3, IgG2a) did not.

Figure 8 Anti-HMBG1 antibody reduces induction of TRAP-5b production by HMGB-1 in osteoclast precursor cultures.

Osteoclast precursor cells stimulated with recombinant HMGB (left panel) or synovial fluid fraction containing HMGB1 (right panel) showed increased TRAP-5b activity. Combination treatment with HMGB1 of either origin with G4 or S16 anti-HMGB1 antibodies but not isotype control antibodies did not result in similar increases