Table 1.
A summary of toxicologic, toxicokinetic, and pharmacodynamic parameters from the various toxicity studies is presented here
| Species (Study) | Epidermal hyperplasia (dose observed) | Biomarkers of target engagement | NOAEL (μg/kg) | % ATA | Doses μg/kg (IV) | C max (ng/mL) | AUC0‐t (ng · day/mL) |
|---|---|---|---|---|---|---|---|
| Rat (11‐week) | Yes (1500 μg/kg) |
|
150 | 24 | 50 | 667 (136) | 547 |
| 150 | 2780 (499) | 2370 | |||||
| 1500 | 32 000 (9680) | 38,000 | |||||
| Miniplg (SC) | Yes (930, 4660 μg) | Not measured | ‐ | ‐ | 930 μg (SC) | 109 (21.4) | 434 (279) |
| 4660 μg (SC) | 929 (123) | 3790 (2650) | |||||
| Miniplg (Wound) | Not measured | ≥318 μg/cm2 :
|
1059 μg/cm2 | 64 μg/cm2 | – | – | |
| 318 μg/cm2 | – | – | |||||
| 1059 μg/cm2 | 7.6 | – | |||||
| Monkey (11‐week) | Yes (≥75 μg/kg) | ≥75 μg/kg:
|
15 | 13 | 15 | 188 (2S.4) | 333 (163) |
| 75 | 1020 (132) | 1890 (581) | |||||
| 300 | 4300 (452) | 7010 (2650) | |||||
| 75 (SC) | 246 | 1009 | |||||
| Monkey (26‐week) | Yes (300 μg/kg) | >100 μg/kg:
|
100 | 20 | 30 | 547 (51.4) | 2350 (343) |
| 100 | 1900 (263) | 8760 (1840) | |||||
| 300 | 5900 (1690) | 36 000 (12 220) |
NOAEL, No observable adverse effect level; ATA, anti‐therapeutic antibody; C max, maximum serum concentration; AUC, are under the curve indicating exposure of drug over time; standard deviation is added in parentheses for mean AUC and C max values (male and female animals combined). “‐” indicates parameter was not determined.