Friday, August 25, 2023
MapLight Therapeutics, a clinical-stage biopharmaceutical company, has successfully completed a second Phase 1 clinical trial for its novel compound ML-007. This compound is designed to target M1/M4 muscarinic receptor agonists with the aim of addressing brain circuit dysfunction associated with neurodegenerative and neurocognitive disorders such as schizophrenia, Alzheimer's disease psychosis, and dyskinesias.
During the study, which involved 106 participants across different healthy adult and elderly cohorts, ML-007 was administered both on its own and in combination with a selective muscarinic antagonist. The objective was to establish dosing strategies that would maximize effectiveness while maintaining tolerability. The trial consistently showed a favorable safety and tolerability profile across all participant groups. Any adverse events observed were generally mild and temporary, and they correlated with dose-dependent effects.
A significant observation was that ML-007 displayed excellent safety and tolerability even at doses exceeding the anticipated effective levels. Combining ML-007 with the muscarinic antagonist resulted in high plasma concentrations of ML-007 being well-tolerated. Importantly, the study did not identify any severe or serious adverse events. Notably, the tolerability of the treatment was comparable between different age groups, spanning both healthy adults and the elderly. This comparability was evident in terms of the type, severity, and duration of adverse events.
The pharmacokinetic data acquired from the study supported the feasibility of administering ML-007 twice daily across various age groups. Additionally, the data affirmed that ML-007 had high permeability, good bioavailability, and exposure levels that increased proportionally with the dosage. Based on these promising findings, MapLight intends to progress to Phase 2 trials, focusing on an extended-release combination of ML-007 and the muscarinic antagonist, with a fixed-dose regimen.
Dr. Erin Foff, Chief Medical Officer at MapLight, underscored the potential of ML-007 as a novel treatment option for conditions like psychosis and dyskinesias, which often lack satisfactory therapies and may pose safety concerns with existing treatments. Dr. Christopher Kroeger, the CEO, highlighted the compound's encouraging safety profile, its positive tolerability, and pharmacokinetic characteristics, all of which suggest its potential efficacy across a spectrum of indications.
The specificity of ML-007 in targeting M1 and M4 muscarinic receptors is particularly significant, as these receptors play a crucial role in regulating neural circuits associated with schizophrenia and cognitive functions linked to psychosis. Schizophrenia, a debilitating mental disorder, often lacks effective treatments, leaving a significant unmet medical need. Dyskinesias, characterized by involuntary muscle movements, can arise from underlying conditions or medication side effects, greatly affecting quality of life. Similarly, Alzheimer's disease psychosis lacks approved treatments, affecting a considerable portion of Alzheimer's patients.
In conclusion, MapLight's ML-007 has demonstrated promising outcomes in its Phase 1 trial, suggesting its potential to address existing medical gaps across a range of brain disorders. The unique mechanism of ML-007 and its favorable safety profile position it as a candidate for further exploration in Phase 2 trials.
