Table 1 In-vitro binding characteristics of SAR2559952, humanized SAR228810, and comparators
Mouse IgG | ELISA Aβ | ELISA aggregated proteins | |||||
EC50 ng/ml | EC50 ng/ml | ||||||
Mean EC50 | Protofibril (soluble) | LMW/monomer | Fibril/aggregates | IAPP fibrils | Synuclein fibrils | ||
SAR255952 | 36 ± 5.5 | 3751 ± 130 | 68 ± 15 | NB up to 100 μg/ml | NB up to 100 μg/ml | ||
3D6 | 61 ± 4.4 | 86 ± 6 | 45 ± 17 | NB up to 100 μg/ml | NB up to 100 μg/ml | ||
Human IgG | ELISA Aβ | ELISA aggregated proteins | SPR | ||||
EC50 ng/ml | EC50 ng/ml | Kd (M) | |||||
Protofibrils (soluble) | LMW/monomer | Aβ fibrils | IAPP fibrils | Synuclein fibrils | Aβ monomer | Aβ protofibrils (soluble) | |
SAR228810 | 37 ± 2 | 14,403 ± 3403 | 16.7 ± 3.4 | NB | NB | NB up to 1000 nM | 4.3 ± 5 × 10–10 |
3D6 human IgG | 32 ± 2 | NA | 7.7 ± 2.2 | NA | NA | 1.7 ± 1 × 10–8 | < 10–10 |
Gantenerumab | 26 ± 8 | NA | 19.9 ± 4.7 | NA | NA | 3.4 ± 3 × 10–5 | 8 ± 3 × 10–10 |
BAN-2401 | 21.3 ± 9 | NA | 15.5 ± 5.1 | NA | NA | 8.7 ± 4 × 10–6 | < 10–10 |