PROJECT SUMMARY
Acute brain injuries resulting from cerebrovascular injury or trauma, such as intracerebral hemorrhage (ICH) or
traumatic brain injury, are major medical problems that cause considerable mortality and morbidity in older
Americans. Secondary neuroinflammatory events after ICH can further damage the brain and lead to increased
risk of neurologic complications including Alzheimer’s disease (AD) and related dementias. Despite significant
advances in the medical management of these patients, there is a clear and urgent need for interventions that
improve neurologic recovery and outcomes. To address this unmet need, the clinical candidate, MW189, is a
CNS-penetrant, small molecule that selectively attenuates injury- and disease-induced proinflammatory
cytokine overproduction. Proinflammatory cytokine overproduction from abnormally activated glia contributes to
cerebral edema, long-term neurological damage, and cognitive deficits following acute brain injuries. This
mechanistic linkage of the acute cytokine surge to progression of injury, plus the attractive therapeutic time
window of hours to days post-insult, provide a rational therapeutic target for intervention in the acute care
setting. The Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) trial is a first-in-patient
phase 2a, proof-of-concept study of MW189 in patients with ICH. The study aims are to: (1) Prepare, recruit,
and conduct the phase 2a clinical study of MW189, and (2) Evaluate safety, pharmacokinetics (PK),
inflammatory biomarkers, and clinical outcomes. This multicenter, prospective, randomized, double-blind
controlled trial will enroll 120 non-traumatic ICH participants, with an anticipated average age in their mid-60s
and substantial numbers of individuals with cerebral small vessel disease and cerebral amyloid angiopathy.
Patients will be randomized to MW189 or placebo in a 1:1 ratio, with the first dose initiated within 24 hours of
symptoms, then dosing every 12 hours for 5 days (or until discharge, whichever is first). Safety and tolerability
of MW189 compared to placebo, and PK profiles of MW189 will be determined. Exploratory outcomes will
include radiographic and clinical endpoints and measurement of plasma levels of brain-derived inflammatory
and neuronal injury biomarkers to demonstrate engagement of pharmacological mechanism. Success with
MW189 in ICH patients will further de-risk the compound for subsequent larger trials of acute CNS injury
and/or to develop the drug for AD and other age-related dementias. The study will also generate important
information about the utility of targeting the acute proinflammatory cytokine aspects of neuroinflammation in
older Americans with vascular disease.