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FigureLegends
Fig.S1 Time-course profiles of bispecific antibody PK and target suppression after multiple dosing (Q2W). Profiles were simulated using model in Fig.1B and parameters in Table D1 for 0.0001 mg/kg (blue), 0.001 mg/kg (red), and 0.01 mg/kg (green) (A-C) and model in Fig.1A and parameters in Table D1 for 0.1 mg/kg (blue), 1 mg/kg (red), and 5 mg/kg (green) (D-F). Profiles for plasma space (solid lines) and tissue space (dashed-lines) are shown. A) Time-course of free plasma and tissue kinetics of bispecific antibody targeted against IL4 and IL13. B) Free plasma and tissue IL4 target suppression. C) Free plasma and tissue IL13 target suppression. D) Time-course of free plasma and tissue kinetics of bispecific antibody targeted against ICOSL and CXCL13. E) Free plasma and tissue CXCL13 target suppression. F) Free plasma and tissue mICOSL target suppression.
Fig.S2 Simulated PK and target suppression profiles for asthmatic conditions after single and multiple dosing. Profiles were simulated using model in Fig.1B and parameters in Table D1 for 0.0001 mg/kg (blue), 0.001 mg/kg (red), and 0.01 mg/kg (green). Profiles for plasma space (solid lines) and tissue space (dashed-lines) are shown. A) Time-course of free BAb after single dose levels. B) Free IL4 target suppression after single dose levels. C) Free IL13 target suppression after single dose levels. D) Time-course of free BAb upon multiple repeated doses (Q2W). E) Free IL4 target suppression upon multiple repeated doses (Q2W). F) Free IL13 target suppression upon multiple repeated doses (Q2W).
Fig.S3 Influence of RD and kint on bispecific antibody kinetics and dynamics. Profiles were simulated using model in either Fig.1B and parameters in Table D1 for 0.01 mg/kg (A-C) or Fig.1A and parameters in Table D1 for 5 mg/kg (D-I). Arrows indicate either increasing RD or kint values. Profiles are shown for plasma (solid lines) and tissue (dashed-lines) spaces. For panels A-C, lines corresponding normal RD value (0.1, blue), 2-fold decrease in RD (0.05, green), 2-fold decrease in RD (0.2, red) are shown. A) Time-course of free BAb directed against IL4 and IL13. B) Free plasma and tissue IL4 target suppression. C) Free plasma and tissue IL13 target suppression. For panels D-F, lines corresponding normal RD value (0.05, blue), 2-fold increase in RD (0.1, red), 4-fold increase in RD (0.2, green) are shown. D) Time-course of free BAb directed against ICOSL and CXCL13. E) Free plasma and tissue CXCL13 target suppression. F) Free plasma and tissue mICOSL target suppression. For panels G-I, lines corresponding normal kint value (0.1, blue), 10-fold decrease in kint (0.01, red), 100-fold increase in kint (0.001, green) are shown. G) Time-course of free BAb directed against ICOSL and CXCL13. H) Free plasma and tissue CXCL13 target suppression. I) Free plasma and tissue mICOSL target suppression.
Fig.S4 Comparison of time-course of combination of single-agents versus bispecific antibody exposure. Profiles were simulated using model in either Fig.1B and parameters in Table D1 for 0.01 mg/kg (A-C) or Fig.1A and parameters in Table D1 for 5 mg/kg (D-F). Plasma space (solid lines) and tissue space (dashed-lines).Bispecific antibody (blue),IL4 or ICOSL single agent (red), and IL13 or CXCL13 single agent (green) profiles are represented. A) Time-course of free plasma and tissue kinetics of bispecific antibody targeted against IL4 and IL13. B) Free plasma and tissue IL4 target suppression. C) Free plasma and tissue IL13 target suppression. D) Time-course of free plasma and tissue kinetics of bispecific antibody targeted against ICOSL and CXCL13. E) Free plasma and tissue mICOSL target suppression. F) Free plasma and tissue CXCL13 target suppression.
Fig.S5 Simulated PK/PD profiles with RD set to 1. A) Time-course of free plasma and tissue mBAb disposition. B) Time-course of free plasma and tissue CXCL13 target suppression. C) Free plasma and tissue sICOSL target suppression. D) Free plasma and tissue mICOSL target suppression. Profiles were simulated using the proposed model in Fig.1A after multiple single doses of 0.1 mg/kg (blue), 1 mg/kg (red), and 5 mg/kg (green). Plasma and tissue profiles are shown as solid and dashed lines. E) Time-course of free plasma and tissue sBAb kinetics. F) Time-course of free dose normalized plasma and tissue kinetics of sBAb. G) Time-course of free plasma and tissue IL4 target suppression. H) Free plasma and tissue IL13 target suppression. Profiles were simulated using the proposed model in Fig.1B after multiple single doses of 0.0001 mg/kg (blue), 0.001 mg/kg (red), and 0.01 mg/kg (green).
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