Toxicokinetics of NIDO-361, a Potential Candidate to Treat Spinal and Bulbar Muscular Atrophy (SBMA), in Rats and Monkeys Following Oral Dosing in a 4-Week Toxicity Study

Purpose

While the underlying genetic causes of many rare diseases have been elucidated, there is still a gap between understanding disease conditions and translating this knowledge to effective treatments. In most circumstances, rare diseases have no cure and limited options for therapeutic intervention. Therefore, supporting advancement of rare disease drug programs through rigorous design of preclinical studies combined with analytical assessment of study outcomes is crucial in addressing this ongoing global health issue. NIDO-361 is a novel small molecule that binds to a distinct site on the androgen receptor (AR) to regulate co-factor binding and thereby corrects transcriptional dysregulation. NIDO361 is currently being investigated for the treatment of patients suffering from Spinal and Bulbar Muscular Atrophy (SBMA); a rare inherited X-linked neuromuscular disorder caused by a genetic mutation of the AR resulting in the loss of skeletal muscle and motor neuron function. In this study, the toxicokinetics (TK) of NIDO-361 was assessed following once-daily oral dosing to male Sprague Dawley rats and male Cynomolgus monkeys. Analysis of NIDO361 plasma concentrations was performed by HPLC/MS/MS and the resulting data sets were used to evaluate the drug exposure profile and to inform dosing decisions for future studies.