TABLE 1.
Exposure to Mim8 in cynomolgus monkeys after weekly administration
| Study | Dose (mg/kg/week) | Administration route | Neutralizing ADA status (n) | Cmax, nmol/L a | Cmax/dose b | AUC0–168 h, h × nmol/L a | AUC0–168 h/dose b |
|---|---|---|---|---|---|---|---|
| 4‐week | 1 | SC | ‐‐ (2) | 150 (11.3) | 150 | 21,700 (9.56) | 21,700 |
| 4 | SC | ‐‐ (2) | 441 (26.9) | 110 | 68,600 (29.5) | 17,200 | |
| 20 | SC | ‐‐ (2) | 1960 (2.16) | 98 | 276,000 (0.574) | 13,800 | |
| 60 | SC | ‐‐ (2) | 7500 (3.77) | 125 | 974,000 (6.81) | 16,200 | |
| 20 | IV | ‐‐ (2) | 4460 (2.85) | 223 | 480,000 (7.17) | 24,000 | |
| 13‐week | 0.3 | SC | ‐‐ (6) | 58.2 (15.3) | 194 | 8840 (16.4) | 29,500 |
| 6 | SC | ‐‐ (4) | 750 (12.1) | 125 | 107,000 (13.9) | 17,800 | |
| + (2) | 30.5 (119) | 5.08 | 1640 (128) | 273 | |||
| 12 c | SC | ‐‐ (7) | 2320 (13.5) | 193 | 352,000 (13.3) | 29,400 | |
| + (3) | 564 (38.6) | 47 | 54,600 (41.5) | 4550 | |||
| 1 | IV | ‐‐ (1) | 306 | 306 | 37,100 | 37,100 | |
| + (5) | 61.7 (90.9) | 61.7 | 1580 (149) | 1580 | |||
| 26‐week | 0.3 | SC | ‐‐ (4) | 81.6 (30.2) | 272 | 12,700 (33.0) | 42,300 |
| + (4) | N/A d | N/A d | N/A d | N/A d | |||
| 1 | SC | ‐‐ (5) | 241 (13.0) | 241 | 36,500 (10.5) | 36,500 | |
| + (3) | N/A d | N/A d | N/A d | N/A d | |||
| 3 | SC | ‐‐ (4) | 730 (3.53) | 243 | 109,000 (2.04) | 36,400 | |
| + (4) | N/A d | N/A d | N/A d | N/A d |
Abbreviations: ADA, anti‐drug antibodies; AUC, area under the curve; Cmax, maximum plasma concentration; h, hours; IV, intravenous; SC, subcutaneous.
a
Cmax and AUC values are presented as the geometric mean (CV%).
b
Normalized to 1 mg/kg.
c
Including exposure after 13 weeks in the 4 recovery animals dosed for 13 weeks followed by a 13‐week recovery phase.
d
In the 26‐week study all ADA‐positive animals had no exposure to Mim8 at the end of the study.