Table 1.

Summary of findings in dose range–finding toxicity and PK study in cynomolgus monkey

Parameter/organ systemEffect
Body weightMaximum transient body weight loss: 8.7% (2nd cycle)
White blood cell populationsMild transient decreases at ≥ 10 mg/kg/cycle
Red blood cell parametersTransient decrease followed by rebound in reticulocytes at ≥ 10 mg/kg/cycle
ThrombocytesNo reduction below 95% confidence intervals of population predose values (NOEL: ≥ 30 mg/kg/cycle)
LiverNo effect on transaminases, albumin, bilirubin, and histopathology (NOEL: ≥ 30 mg/kg/cycle)
Peripheral neuropathyNo effects on behavior and histopathology (NOEL: ≥ 30 mg/kg/cycle)
OvariesMild effects in line with target expression
SkinHyperpigmentation at dosages ≥ 10 mg/kg/cycle. Reversible facial swelling in 1 animal at 10 mg/kg/cycle.