Storm: proof-of-concept studies of oral MW189, a novel anti-neuroinflammatory drug, in alzheimer's patients

The National Institute on Aging awarded The Johns Hopkins University a cooperative agreement valued at $4,039,776 on September 1, 2026, to conduct proof-of-concept clinical studies of MW189, an oral anti-neuroinflammatory therapeutic candidate, in patients with amnestic mild cognitive impairment and early Alzheimer's disease under the Aging Research program (CFDA 93.866).

MW189 is a first-in-class glial cytokine normalizer targeting the neuroinflammation-synaptic dysfunction axis. The recipient will execute a two-part trial: Part 1 will be a short proof-of-concept dose-finding study of MW189; Part 2 will extend to 12 months of daily oral administration. The primary objective is to test safety and tolerability of repeat oral administration in patients. Secondary and exploratory objectives include confirmatory dose-dependent drug exposure by pharmacokinetics and biomarkers of neuroinflammation and synaptic dysfunction. MW189 has demonstrated efficacy in preclinical models of Alzheimer's disease, shows a high safety margin in extended toxicology studies, and is well-tolerated in healthy adult clinical safety trials and a current Phase 2A trial in hemorrhagic stroke patients. This will be the first clinical evaluation of repeat daily oral administration of MW189 in Alzheimer's patients.

Work is performed at Baltimore, Maryland, with a period of performance from September 1, 2026, through August 31, 2028.

Abstract

Neuroinflammation in the CNS is a complex set of responses that is now recognized as an early and critical contributor to the pathogenesis of many neurodegenerative disorders, including alzheimer's disease (ad). While some neuroinflammatory responses are beneficial, overproduction of proinflammatory cytokines by chronically activated brain immune cells, especially microglia and astrocytes, drives neurodegenerative processes and results in cognitive impairment. There is a lack of well-tolerated disease-modifying therapeutics addressing cytokine normalization. MW189 is a first-in-class, glial cytokine normalizer that targets the neuroinflammation-synaptic dysfunction axis. IT offers potential complementary utility alongside anti-amyloid drugs and applicability across both chronic (e.g., alzheimer's disease) and acute (e.g., intracerebral hemorrhage) indications. Our small molecule therapeutic candidate, MW189, is efficacious in preclinical models of ad, shows a high safety margin in extended toxicology studies, and is well-tolerated in healthy adult clinical safety trials. Further, MW189 is safe and well tolerated in a current phase 2A trial in hemorrhagic stroke patients. The proposed project, "storm: proof-of-concept studies of oral MW189, a novel anti-neuroinflammatory drug, in alzheimer's patients", will be the first clinical evaluation of repeat daily oral administration of MW189. We propose to test MW189 in patients with amnestic mild cognitive impairment (MCI)/ early ad in a two-part trial. Part 1 will be a short proof-of-concept dose-finding study of MW189; part 2 will be a more extended 12-month daily oral administration of MW189. The primary objective is to test the safety and tolerability of MW189 repeat oral administration in patients. Secondary/exploratory objectives will include confirmatory dose dependent drug exposure by pharmacokinetics, cognitive function tests, MRI for hippocampal atrophy and white matter hyperintensities, and plasma assays for alzheimer's biomarkers and pharmacodynamic endpoints. This proposed project is in response to PAR-25-226 and includes the following specific aims: aim 1: perform trial start-up activities, including production of GMP clinical drug compliant for oral repeat administration patient trials (API); clinical documents and regulatory approvals (IND/IRB); and clinical site training and activation. Aim 2: conduct the part 1 proof-of-concept dose-finding study of MW189. Aim 3: conduct the part 2 clinical study of MW189. Deliverables/milestones and go/nogo decision points are included in the study. Success in this proposed proof-of-concept trial will allow future progression into the next phase of clinical development trials for ad or other related dementias.