Anti-Human DKK1 Recombinant Antibody (huMabJC18) (CAT#: TAB-193MZ)

Figure 1 shows the specificity of binding of JC18 to human homologues Dkk-1, Dkk-3 and Dkk-4.

JC18 showed weak binding to human Dkk-4 and no binding to human Dkk-3 up to 5 ug/ml.

Figure 2 shows a graph of observed and model predicted free/partially free huMabJC18 concentrations versus time following weekly intravenous administration of huMabJC18 to Sprague-Dawley rats.

Symbols represent the mean observed data (±SD) and lines represent the predicted profiles from the model.

Figure 3 show graphs of observed and model predicted free/partially free huMabJC18 concentrations versus time following single intravenous administration of huMabJC18 to Cynomolgous monkeys.

(A) Male monkeys. (B) Female monkeys. Symbols represent the observed individual monkey data and lines represent the predicted profiles from the model.

Figure 4 shows a graph of mean osteocalcin concentrations (±SE) at 1.5 and 2.5 weeks post first dose following weekly intravenous administration of huMabJC18 to Sprague-Dawley rats. * indicates p<0.05 vs. vehicle

Figure 5 shows a graph of predicted free Dkk-1 concentrations in humans following subcutaneous administration of huMabJC18 1/month for 6 months.

Three different doses were tested: 0.003 mg/kg which represents 1/10 of MABEL or a no effect dose, 0.03 mg/kg which represents MABEL and 3.57 mg/kg which represents predicted efficacious dose for osteoporosis.

Figure 6 shows a graph of predicted free huMabJC18 concentrations in humans following subcutaneous administration of huMabJC18 1/month for 6 months.

Three different doses were tested: 0.003 mg/kg which represents 1/10 of MABEL or a no effect dose, 0.03 mg/kg which represents MABEL and 3.57 mg/kg which represents predicted efficacious dose for osteoporosis. Anticipated Limit of Quantitation (LOQ) of the bioanalytical assay is shown to represent the futility of dosing lower than predicted MABEL.

Figure 7 shows a graph of receptor occupancy calculations for huMabJC18 vs.

predicted human dose based on (1) steady state equilibrium method (Duff, 2006) and (2) mechanistic PK/PD (TMDD) model.