Characterization and Potential Mitigation of Corneal Effects in Nonclinical Toxicology Studies in Animals Administered Depatuxizumab Mafodotin.

To characterize the ocular toxicity of an antibody-drug conjugate (ADC), depatuxizumab mafodotin (Depatux-m), in nonclinical species and to evaluate the effects of drug-antibody ratios (DARs), variations of the ADC construct, and potential methods for mitigation of the corneal toxicity. Depatux-m contains the potent cytotoxic agent monomethyl auristatin F as the ADC payload. Depatux-m was administered intravenously to cynomolgus monkeys at doses up to 30 mg/kg and to mice up to 100 mg/kg.

Left thoracotomy surgical approach for chronic instrumentation in dogs and monkeys providing high-quality electrocardiogram signals.

Introduction: Assessment of cardiovascular parameters, including the electrocardiogram (ECG) is required by the regulatory guidelines. In safety pharmacology studies, this is typically done using chronically implanted radiotelemetry devices in non-rodent species.

Methods: We compared ECG signal quality from ten male beagle dogs and 10 male cynomolgus monkeys with telemetry transmitters implanted using two surgical approaches: i) epicardial ECG lead placement via single incision, left side thoracotomy or ii) subcutaneous ECG lead placement via laparotomy.

Orchidectomy, but not ovariectomy, regulates angiotensin II-induced vascular diseases in apolipoprotein E-deficient mice.

In humans, the incidence and severity of abdominal aortic aneurysms (AAA) are greater in males than in females. Chronic infusion of angiotensin II (AngII) into apolipoprotein E-deficient (apoE(-/-)) mice promotes atherosclerosis and causes the formation of AAAs. Just as human males are more susceptible to developing AAAs, male mice are more susceptible to AngII-induced AAAs.