MapLight Therapeutics Reports Phase 1 Trial Results for M1/M4 Muscarinic Agonist for Schizophrenia and Alzheimer's Psychosis

MapLight Therapeutics, a clinical-stage biopharmaceutical company, shared results from its Phase 1 trial of ML-007/PAC, assessing safety, tolerability, and pharmacokinetics in healthy adults and elderly volunteers. ML-007 has been evaluated as a single agent and in combination with a peripherally acting anticholinergic (PAC) across four Phase 1 trials involving 270 subjects. The company aims to commence Phase 2 trials for schizophrenia and Alzheimer's disease psychosis (ADP) in the first half of 2025.

Christopher Kroeger, M.D., M.B.A., CEO and Founder of MapLight, emphasized the significance of the new class of muscarinic agonists in addressing various brain disorders. ML-007/PAC has shown a favorable safety and tolerability profile with both once- and twice-daily dosing, achieving anticipated clinically relevant exposures. Kroeger noted that ML-007/PAC could potentially become a leading M1/M4 muscarinic agonist, offering improved tolerability, convenient dosing, and comprehensive symptom improvement.

The study design involved 82 healthy adult and elderly volunteers across four cohorts, with subjects dosed for up to 14 days. This was aimed at informing the dosing regimen for the planned Phase 2 trials in schizophrenia and ADP. The results indicated that ML-007/PAC was generally well tolerated at doses planned for Phase 2 trials. Most treatment-emergent adverse events (TEAEs) were mild and transient, with no severe or serious adverse events reported. Plasma and cerebrospinal fluid (CSF) exposures remained above anticipated clinically relevant levels with both dosing regimens. The plasma concentration ratio between ML-007 and PAC was within the target range to minimize adverse events. Pharmacokinetic parameters were similar between adult and elderly volunteers, confirming that dosing for Phase 2 trials will not require administration in a fasted state.

Erin Foff, M.D., Ph.D., Chief Medical Officer of MapLight, expressed confidence in progressing to the next phase of development. The Phase 1 trials provided critical data for finalizing dosing and administration protocols for Phase 2 trials in schizophrenia and ADP, moving closer to offering a better treatment option for patients and caregivers.

ML-007/PAC, also known as ML-007C-MA, is an extended-release, fixed-dose combination of the investigational M1/M4 muscarinic agonist ML-007 and a peripherally acting anticholinergic (PAC). Its potential differentiation lies in the optimized pharmacokinetic synchronization of its agonist and antagonist components in the periphery, without compromising strong activation of M1 and M4 receptors in the central nervous system.

MapLight Therapeutics aims to improve the lives of patients with debilitating central nervous system disorders. Founded by leaders in psychiatry and neuroscience research, the company seeks to address the lack of circuit-specific pharmacotherapies. Their discovery platform identifies neural circuits linked to diseases and targets these circuits for therapeutic modulation.