MapLight Therapeutics plans to start Phase II trials to evaluate the combination treatment of M1/M4 muscarinic receptor agonist (ML-007) and antagonist for the treatment of multiple neurodegenerative and neurocognitive disorders in 2024.
The news follows MapLight’s announcement of completing a second Phase I trial for ML-007 in healthy volunteers. The study included a cohort of patients who received the ML-007 and muscarinic antagonist combination treatment. The first Phase I trial investigating Ml-007 in healthy volunteers was completed a year ago.
Muscarinic receptors are involved in multiple central and peripheral parasympathetic functions. The receptor's peripheral functions include micturition, bronchoconstriction, and salivation. MapLight’s combination therapy is designed to neutralise the peripheral activity of muscarinic receptors and only produce a central effect.
ML-007 is a muscarinic receptor agonist that targets M1 and M4 subtypes of the receptor. These subtypes have no direct effect on dopamine receptor activity. M1 receptor activity has been associated with schizophrenia, psychosis, and cognition. In contrast, M4 receptors play a role in psychosis by regulating the complementary neural pathway.
"Currently available treatments do not adequately address the needs of people experiencing psychosis or dyskinesias related to drug treatment. These medications can have intolerable side effects and lead to significant safety concerns for some patient populations, particularly older patients," said MapLight's chief medical officer, Erin Foff in a press release.
"This study generated crucial data to help inform further development of ML-007 as a novel option for patients with these conditions. We are extremely encouraged by the safety profile observed in both younger and older subjects."
The randomised, placebo-controlled Phase I trial enrolled 106 healthy adults and elderly volunteers across ten and three cohorts, respectively. The pharmacokinetic data showed drug exposure to ML-007 increased proportionally with dosage increases. Additionally, the drug showed high permeability and bioavailability.
ML-007 was well-tolerated, with mild adverse events at twelve times the minimum plasma concentration when paired with muscarinic antagonists. The trial reported no severe or serious adverse events.
MapLight plans to investigate ML-007 in multiple indications including schizophrenia, Alzheimer's disease psychosis, and dyskinesias.
