Novel anti-neuroinflammatory drug for aneurysmal subarachnoid hemorrhage (aSAH)

点击翻译按钮获取中文摘要

ABSTRACT Nontraumatic (aneurysmal) subarachnoid hemorrhage (aSAH) is one of the most dangerous forms of stroke, with almost half of victims dying within the first month after diagnosis, and a half of the survivors becoming severely disabled and incapable of living independently. This proposal is focused on addressing a common pathophysiological mechanism of neurocognitive outcomes of aSAH and other acute and chronic brain injuries – dysregulated overproduction of proinflammatory cytokines in the brain. Despite advances in our understanding of molecular neuroinflammatory mechanisms underlying adverse neuronal sequelae of acute and chronic brain injuries, approved therapeutics that target this pathological process are lacking. ImmunoChem Therapeutics (ICT) proposes to advance MW189, a novel small molecule anti-inflammatory experimental drug which has already successfully completed phase 1a and phase 1b clinical trials, as a candidate for a disease-modifying therapy for aSAH. MW189 is a selective suppressor of injury- and disease- induced proinflammatory cytokine overproduction associated with destructive glia inflammation/synaptic dysfunction cycles and their long-term neurotoxic effects. This proposed Fast-Track SBIR will deliver a phase 2a trial-ready drug and the corresponding regulatory documentation portfolio for a future pilot trial in aSAH. Specifically, we will: 1. Extend preclinical efficacy and pharmacodynamic data, and obtain the dosing and drug exposure information required to support a future phase 2a proof-of-concept clinical study in aSAH patients; 2. Produce and validate a GMP batch of the drug product from the existing cGMP drug substance (API) supply at a qualified Contract Manufacturing Organization (CMO); and 3. Prepare and submit an amendment to the open MW189 IND for a phase 2a clinical trial in aSAH patients. The Fast-Track structure will allow us to immediately move from proof of feasibility to SBIR Phase II activities that flow seamlessly from preparation of the Phase 2 trial-ready drug product to essential regulatory milestones for a future first-in-patient aSAH trial. Successful execution of the proposed project will position MW189 for immediate entry into a pilot proof-of-concept phase 2 trial in aSAH patients that will include pharmacokinetics and a pharmacodynamic arm. The success in that trial will, in turn, make MW189 a first-in-class drug candidate with a potential to become a novel therapeutic approach to SAH and other acute and chronic neurological disorders that involve dysregulated neuroinflammation as a driver of disease progression.