This document outlines the design of a dose escalation and tolerability study to test new drug candidates. It describes initiating testing at a starting dose based on prior data, then gradually increasing the dose in increments until the maximum tolerated dose is found. Throughout the study, clinical chemistry, hematology, and organ pathology will be monitored to assess safety and detect any adverse effects.

1. Dose Escalation / Tolerability Study Design
• Dose route: Oral, IV bolus, subcutaneous, intraperitoneal, intramuscular, dermal, topical
• Dose used: Initiate starting dose based on in vitro cytotoxicity and/or published literature. If MTD is not determined
industry standard dose escalation with increments for rapid (1.8x) or slow (1.15x) escalations are used.
• Clinical Chemistry Panel: Albumin, Alkaline Phosphatase, Bilirubin/Total, BUN, Calcium, Chloride, Cholesterol,
Protein/Total, Creatinine, Sodium, ALT, AST, Phosphorus, Potassium, Glucose, GGT, Uric Acid, Triglycerides
• Hematology Parameters: Automated WBC, RBC, Hgb, Hct, Platelet Count, MPV, MCV, MCH, MCHC, and WBC
• Gross Necropsy: To examine the organs for potential abnormalities and lesions
• Histology / Immunohistochemistry: H&E and other specialized staining