Abstract

Safety Evaluation of Biotechnology-derived Immuno-Oncology Therapies, Considerations in Species Selection for Pre-Clinical Testing

Stephen Kirk, Non-Clinical Immunotoxicologist, Covance Laboratories Ltd

Regulatory guidance requires pre-clinical evaluation of immuno-oncology therapies prior to first in human (FIH) trials. Evaluation of such drug candidates can pose many challenges when the compound is a biotechnology based product. Often biotech products are highly specific for human targets and bind the equivalent target in pre-clinical species with much lower affinity or the presence of the target in healthy pre-clinical toxicology species is expressed at much lower levels, or is absent, when compared to the disease state in humans. The intended pharmacological activity of the therapy, such as immuno-stimulation for check-point inhibitors, is only observed when the target is present above certain levels, making exaggerated pharmacology difficult to evaluate in the pre-clinical space. This presentation looks at the challenges of selecting suitable species for pre-clinical evaluation, covering topics such as the use of transgenic mouse models, homologues versus the human drug candidate, overcoming anti-drug antibody challenges and supplementation of in vivo work with in vitro / ex vivo cell based assays.