Preclinical Results: Canine Phase I Safety Study of CM-101, a Tumor Capillary Specific Streptococcal Polysaccharide Toxin, for application in Spontaneous Canine Cancer

Background The study purpose was to evaluate canine safety of CM101, a polysaccharide Group B Streptococcus agalactiae tumor hemorrhagic toxin therapeutic. Hypothesis CM101 specifically targets tumor vasculature as published in a human Phase 1 safety study that showed a wide therapeutic window. The hypothesis is that dogs should display a similar safety profile with low side-effects for CM101 canine cancer therapeutics. Animals Considering the previous human safety trial, and in the interest of conserving purpose-bred dogs, on advice of USDA staff, we only used two healthy males, ∼20 months old. Methods USDA advice was to administer 10x the unit dose of 7.5µg/kg to 2 dogs and if no side effects, proceed to a pilot phase II. Given the dose was 10X the effective unit dose in humans, a further dose escalation was not considered necessary. Dogs were given 10 units (75 µg/kg) CM101 in normal saline over 22 minutes intravenously. Blood and Urine were collected before infusion, intervals post infusion, and 2 weeks after. Under anesthesia through recovery, rectal temperature, heart rate and indwelling arterial blood pressure vital signs were monitored electronically. Clinical observations recorded through two weeks after infusion. Results Total WBC (white blood cell) counts dropped below normal range two hours post-infusion, after 6-11 hours rising above the normal range, returning to baseline at 52 hours post-infusion. Creatinine kinase was elevated two hours post infusion returning to baseline in 6-72 hours. Urinalysis remained within normal limits. Conclusions and clinical importance No adverse effects were observed when healthy dogs were given 10 units CM101. These finding suggest a wide therapeutic window for investigation in canine cancer.