NKT's current lead clinical asset is MW150, a unique and orally bioavailable p38MAPK inhibitor that exhibits brain exposure and efficacy in diverse CNS disease models. The models include tauopathies, Alzheimer's disease and related dementia, and neuropsychiatric disorders characterized by neuroinflammation and synaptic dysfunction. There are no approved drugs or drugs at clinical trial stage with MW150's unique profile of molecular recognition, pharmacological selectivity and safety. Therefore, MW150 has the potential to provide a new therapeutic intervention mechanism for neurologic disease modification.
Clinical Safety and Disease Alteration Potential:
MW150 exhibited exceptional safety, was well-tolerated and provided excellent exposure when administered daily as an oral drug to healthy volunteers. Currently, MW150 is being evaluated in Alzheimer's disease (AD) patients. MW150's mechanism of action allows for pursuit of other disorders where inflammation or synaptic dysfunction are linked to disease progression. For example, published studies in non-clinical models clearly identify certain forms of Autism Spectrum Disorders as a logical candidate.
The neuroinflammation-synaptic dysfunction hypothesis posits that certain aspects of this pathophysiology progression axis are amenable to therapeutic intervention. For example, increased drug target activity in activated glia, endogenous brain immune cells, results in dysregulated innate immunity as evidenced by increased levels of proinflammatory cytokines, small protein regulators of brain function and neuronal homeostasis. Excessive or prolonged increases in certain cytokines can result in neuronal dysfunction. Increased drug target activity in neurons results in altered axonal transport and dysfunction of communication between neurons, as evidenced by altered brain and cognitive function. Neuronal dysfunction, in turn, is detected by glia and results in further stimulation of the evolving stress cycle. The druggable stress kinase, p38MAPK, is a key target in the neuroinflammation-synaptic dysfunction axis. Concurrent inhibition by a highly selective p38MAPK inhibitor of a single molecular drug target in both glia and neurons addresses pathophysiology progression through a novel form of pleiotropic intervention with increased potential for efficacy.
Additional small molecule candidates in pre-clinical drug development represent complementary disease intervention approaches.