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