Phase 1b MAD Study of a Novel Drug (MW189) Targeting Neuroinflammation

A critical mechanism driving neurodegenerative disease progression is dysregulated inflammation in the brain. Neuroinflammatory repair processes are fundamental to CNS homeostasis, but inflammation that is inefficient, excessive, or prolonged can contribute to neurodegeneration. Dysregulated neuroinflammation responses such as proinflammatory cytokine overproduction from abnormally activated glia are seen in both acute conditions with neurodegenerative morbidity such as traumatic brain injury (TBI) and progressive neurodegenerative disorders such as Alzheimer’s disease (AD). This raises the hypothesis that selective attenuation of the dysregulated cytokine response, a component of the neuroinflammation that contributes to neuronal dysfunction, might be an effective component of a multi-faceted therapeutic approach. MW189 is a CNS-penetrant, small molecule drug candidate that selectively suppresses disease- and injuryinduced glial activation and proinflammatory cytokine increases, with downstream improvement in behavior/synaptic function in multiple animal models of CNS disorders such as AD, TBI, and ICH. MW189 has surpassed key development milestones, including preclinical IND-enabling pharmacokinetic (PK)/toxicology, and first-in-human studies (phase 1a single ascending dose trial and a pilot phase 1 study), with no safety issues. A new batch of MW189 drug product is available, and we have an open IND #124357 to proceed with the proposed phase 1b. We anticipate that MW189 will exhibit attractive safety and PK parameters to enable a future phase 2a study in patients.