MapLight Therapeutics, a clinical-stage biopharmaceutical company specializing in the development of targeted therapeutics for brain disorders, has successfully completed a second Phase 1 clinical trial assessing the safety and efficacy of ML-007, a novel M1/M4 muscarinic receptor agonist. The study focused on brain circuits associated with neurodegenerative and neurocognitive disorders such as schizophrenia, Alzheimer's disease psychosis, and dyskinesias. Additionally, the trial explored the combination of ML-007 with a muscarinic antagonist, chosen for its peripheral selectivity and pharmacokinetic properties. This precision pairing aimed to enhance the tolerability profile and support the company's strategy to develop a single, twice-daily combination tablet of ML-007 and the antagonist for both adult and elderly patients.

The Phase 1 trial was randomized and divided into three parts, involving a total of 106 subjects across various healthy adult and elderly cohorts. The study evaluated both single and multiple oral doses of ML-007 alone and in combination with the muscarinic antagonist. The results indicated a consistently positive safety and tolerability profile across all cohorts, with adverse events being generally mild, transient, and correlated with dose escalation effects.

ML-007 demonstrated safety and tolerability across all doses when administered alone, even at levels exceeding clinically relevant exposures. When combined with the muscarinic antagonist, ML-007 was well tolerated even at plasma concentrations twelve times higher than the minimum target level. No severe or serious adverse events were observed during the study. Importantly, the tolerability of multi-dose regimens was comparable between elderly and healthy adult cohorts.

The pharmacokinetic data obtained from the study supported the feasibility of twice-daily dosing across different age groups. MapLight intends to advance a fixed-dose, extended-release combination of ML-007 and the muscarinic antagonist to Phase 2 studies in the following year, maintaining the twice-daily dosing regimen across age groups.

Dr. Erin Foff, Chief Medical Officer of MapLight, emphasized the significance of these results for patients with conditions related to psychosis or dyskinesias, particularly in older patient populations. The positive safety profile observed in both younger and older subjects is encouraging for the development of ML-007 as a novel treatment option.

Christopher Kroeger, Chief Executive Officer and Founder of MapLight, underscored the potential of ML-007 to target M1 and M4 receptors with an appealing safety, tolerability, and pharmacokinetic profile. The company is exploring the broad utility of ML-007 across various indications as it progresses its Phase 2 development plan.

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