Table 4.
Predicted human clearance for ADC conjugate analyte using scaling from only cynomolgus monkey PK data with different fixed exponents of CL
| ADC | Observed CL (mL/day/kg) | Scaling from cyno data using a fixed exponent of CL of 0.75 | Scaling from cyno data using a fixed exponent of CL of 0.85 | Scaling from cyno data using a fixed exponent of CL of 1 | |||||
|---|---|---|---|---|---|---|---|---|---|
| Cyno | Human | w a | CLpred | PE (%) | CLpred | PE (%) | CLpred | PE (%) | |
| DMUC5754Ab | 28.4 | 25.7 | 0.966 | 13.4 | −91.8 | 18.1 | −42.0 | 28.4 | 10.5 |
| DNIB0600Ab | 25.1 | 18.0 | 0.889 | 11.9 | −51.3 | 16.0 | −12.5 | 25.1 | 39.4 |
| DEDN6526Ab | 18.3 | 22.0 | 1.06 | 8.67 | −154 | 11.7 | −88.0 | 18.3 | −20.2 |
| DMOT4039Ab | 30.0 | 27.0 | 0.965 | 14.2 | −90.1 | 19.1 | −41.4 | 30.0 | 11.1 |
| DSTP3086Sb | 26.0 | 17.4 | 0.866 | 12.3 | −41.5 | 16.6 | −4.82 | 26.0 | 49.4 |
| ADC2b | 21.0 | 17.6 | 0.942 | 9.91 | −77.6 | 13.4 | −31.3 | 21.0 | 19.3 |
| T‐DM1c | 10.1 | 8.68 | 0.950 | 4.78 | −81.6 | 6.44 | −34.8 | 10.1 | 16.4 |
| Brentuximab vedotinc | 18.5 | 23.9 | 1.09 | 8.75 | −173 | 11.8 | −103 | 18.5 | −29.2 |
| APE | 95.1 | 44.7 | 24.4 | ||||||
| RSS | 860 | 399 | 197 | ||||||
ADC, antibody–drug conjugate; APE, average absolute value of percentage prediction error (|PE|); CL, clearance; cyno, cynomologus monkeys; PE, percentage prediction errors, which was calculated by ((CLhuman, predicted − CLhuman, observed)/CLhuman, observed) × 100% for overprediction and ((CLhuman, predicted − CLhuman, observed)/CLhuman, predicted) × 100% for underprediction; PK, pharmacokinetic; RSS, residual sum of square.
aThe exponent w for the conjugate were back calculated based on the observed mean CL in cyno and in humans, mean ± SD of w = 0.966 ± 0.077. bConjugate was measured as conjugated drug; cConjugate was measured as conjugated antibody.