Non-clinical development of ozanezumab: a humanised antibody targeting the amino terminus of neurite outgrowth inhibitor A (Nogo-A)

Ozanezumab (GSK1223249) is a humanised, Fc-disabled, monoclonal antibody (mAb) which targets the amino terminus of Neurite Outgrowth Inhibitor A (Nogo-A) which is currently being developed for the treatment of amyotrophic lateral sclerosis (ALS). Here we report on the biochemical and structural characterisation of Ozanezumab together with an assessment of pharmacology and non-clinical safety. A minimal binding epitope was characterised and emerging biology and pre-clinical pharmacology provide confidence that targeting the amino terminus of the neurite outgrowth inhibitor A (Nogo-A) through passive immunization may offer a promising approach to treat various neurodegenerative diseases, including ALS. A comprehensive non-clinical assessment of safety has been completed based on a package of in vitro and in vivo studies in rodents, non-human primates and female rabbits (reproductive toxicology only). There was no evidence for toxicological, cardiovascular, respiratory, neurobehavioural, immunogenic, reproductive or delayed toxicity effects in any species following repeat dose treatment with Ozanezumab (biweekly up to doses of 500 mg kg(-1) iv for 52 weeks in the non-human primate). Based on these studies there are no non-clinical safety findings that would preclude the development of Ozanezumab in patients.