Phase I Enabling
ADME & Toxicology
Risk-managed nonclinical package supporting FIH readiness.
99%Plasma Protein Binding
~3.3mL/min/g Clearance
10 mgStarting Dose
IV
01
ADME Profile
- 99% plasma protein binding
- Moderate intrinsic clearance (human liver microsomes: ~3.3 mL/min/g)
- Minimal CYP450 inhibition
- Poor intestinal permeability → supports IV strategy
- Not a significant P-gp substrate
02
GLP Toxicology
- 29-day IV toxicology studies:
- Rat NOAEL: 1 mg/kg/day
- Cmax ~143 ng/mL
- AUC ~174 ng·h/mL
- Dog NOAEL: 33 mg/kg/dose
- Rat NOAEL: 1 mg/kg/day
- Toxicities:
- Dose-related
- Primarily reversible renal and infusion-site effects
- Data supported a conservative human starting dose of 10 mg
From a buyer’s perspective, this reflects disciplined risk management at FIH entry.