SBIR-STTR Award

ADD234037 belongs to a chemically distinct series of compounds with demonstrated antiepileptic activity. Nonclinical studies with ADD234037 demonstrated that it is active against MES-induced seizures in mice and rats, effective in the rat hippocampal kindling model of partial seizures, and active against sound- induced seizures in the Frings mouse. Based on data generated to date, the overall anticonvulsant and mechanistic profile of ADD234037 is unique when compared to the established antiepileptic drugs. Acute and subacute intravenous toxicity studies in rats and dogs and a 30-day oral toxicity study in rats have demonstrated that daily administration of ADD234037 was not associated with any obvious indications of toxicity which would preclude its further development. The goal of Phase I will be to assess the suitability of ADD234037 for clinical development for the treatment of epilepsy by confirming its favorable activity in models of status epilepticus and assessing the safety of ADD234037 in subacute intravenous toxicity studies in the rat. Mutagenic potential will be determined in a bacterial reverse mutation assay and a mouse micronucleus assay. Favorable results from these studies will prompt initiation of SBIR Phase II which includes the conduct of initial tolerance and kinetic studies in man.

The objective of this application is to determine whether harkoseride (ADD 2340037) is potentially a safe and effective treatment for epilepsy. Specifically, two clinical studies are proposed to achieve this objective. The first is an open-label ascending dose proof of principle study in a limited number of patients to assess pharmacokinetics, potential drug interactions, and safety in this population and to give an indication of efficacy and a rough estimate of dose. From the information gained in this first study, a double blind placebo controlled second study will be designed to establish an optimal, effective dose and to statistically determine whether harkoseride is a clinically effective and safe agent. Based on nonclinical efficacy and mechanism of action studies and clinical pharmacokinetic and tolerability studies to date, harkoseride has demonstrated a unique mechanism, an ideal pharmacokinetic profile, and acceptable safety margin to be a major contribution to the treatment of epilepsy, PROPOSED COMMERCIAL APPLICATION Harkoseride (ADD 234037) has demonstrated an excellent safety, efficacy, and pharmacokinetic profile in nonclinical and clinical studies. Its broad ramp of activity, unique mechanism(s) of action, and availability of both an oral and parenteral formulation make a most promising compound for further development to treat epilepsy, a disease which is not completely controlled with existing medication