MEM-1003 (BAY Z 4406): A Clinical Development and Discontinuation Analysis of an L-type Calcium Channel Modulator for CNS Disorders

1. Executive Summary

MEM-1003, also identified by the synonym BAY Z 4406, was an investigational small molecule drug belonging to the dihydropyridine chemical class, specifically optimized for central nervous system (CNS) applications.[1] It was developed by Memory Pharmaceuticals Corp. with the primary therapeutic goals of treating Alzheimer's disease and acute mania associated with bipolar disorder.[3] The core mechanism of action for MEM-1003 centered on its function as an L-type calcium channel modulator, intended to normalize aberrant calcium signaling within neurons, a pathological feature implicated in various CNS conditions.[3]

Preclinical investigations yielded promising results, suggesting that MEM-1003 could enhance cognitive functions in animal models of aging and Alzheimer's disease and exhibited a degree of CNS selectivity by preferentially affecting cerebral vasculature over peripheral systems.[5] Early-phase human trials further established a generally favorable safety and tolerability profile for MEM-1003, with no significant adverse cognitive effects noted in Alzheimer's patients at the doses tested.[7]

Despite these encouraging early findings, the clinical development program for MEM-1003 ultimately encountered insurmountable efficacy hurdles. Two pivotal Phase 2a clinical trials, one in Alzheimer's disease (NCT00257673) and another in bipolar mania (NCT00374920), failed to achieve their primary efficacy endpoints.[2] The Alzheimer's study was notably confounded by a significant placebo response, while the bipolar mania study showed no therapeutic benefit over placebo.[2] Consequently, due to this lack of demonstrated clinical efficacy, the development of MEM-1003 was discontinued.