SAN FRANCISCO and BOSTON, July 27, 2026
MapLight Therapeutics announced positive topline results from its Phase 2 ZEPHYR clinical trial evaluating ML-007C-MA, an investigational oral M1/M4 muscarinic agonist developed for adults experiencing an acute exacerbation of schizophrenia. The study achieved its primary endpoint, with the 210/3 mg twice-daily (BID) dose demonstrating a statistically significant improvement in Positive and Negative Syndrome Scale (PANSS) total score compared with placebo after five weeks of treatment. The therapy produced an effect size of 0.37, with a 4.5-point improvement in PANSS score (p=0.015), while also showing encouraging improvements across several secondary efficacy measures. Based on these findings, the company plans to engage with the U.S. Food and Drug Administration (FDA) during an End-of-Phase 2 meeting to discuss the design of a registrational Phase 3 program..
Phase 2 Trial Demonstrates Significant Efficacy and Cognitive Benefits
The ZEPHYR trial enrolled 307 adult patients across 25 U.S. clinical sites, comparing placebo with twice-daily and once-daily dosing regimens of ML-007C-MA. Beyond meeting the primary endpoint, the 210/3 mg BID dose achieved statistically significant improvements in several key secondary endpoints, including Clinical Global Impression of Severity (CGI-S) and the PANSS Positive Marder Factor. Importantly, the investigational therapy also demonstrated a clinically meaningful improvement in cognitive performance among participants with baseline cognitive impairment, achieving an effect size of 0.51 (p=0.041). The cognitive improvements appeared to be independent of reductions in psychotic symptoms, suggesting the therapy may address one of schizophrenia’s most challenging unmet medical needs. The higher 330/6 mg once-daily dose showed numerical improvements across multiple endpoints but did not achieve statistical significance for the primary endpoint.
Favorable Safety Profile Supports Long-Term Treatment Potential
ML-007C-MA was generally well tolerated across both dose groups, with no serious adverse events or drug-related severe adverse events reported during the study. Most treatment-emergent adverse events were mild and cholinergic in nature, while gastrointestinal side effects rarely resulted in treatment discontinuation. Investigators also reported low rates of anticholinergic complications, with no clinically meaningful signals involving urinary retention, metabolic abnormalities, liver toxicity, extrapyramidal symptoms, or blood pressure changes. Additionally, the therapy requires no fasting restrictions and only a single-dose titration, features that may improve patient adherence in routine clinical practice. These safety findings complement the encouraging efficacy results and strengthen the potential of ML-007C-MA as a differentiated treatment option for schizophrenia.
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Company Plans Registrational Development Following FDA Discussions
Following the successful Phase 2 ZEPHYR trial, MapLight Therapeutics intends to meet with the FDA to finalize plans for a Phase 3 registrational study, which would serve as a confirmatory trial supporting a future New Drug Application (NDA). The company has already begun planning the study and identifying clinical sites while continuing development of additional dosing strategies, including a potential once-daily regimen. Beyond schizophrenia, the same 210/3 mg BID dose is currently being evaluated in the VISTA trial for hallucinations and delusions associated with Alzheimer’s disease psychosis, with topline data expected in the second half of 2027. These positive Phase 2 findings further strengthen MapLight’s central nervous system pipeline and position ML-007C-MA as a promising investigational therapy with the potential to improve both psychotic symptoms and cognitive impairment in schizophrenia.
Source: MapLight Therapeutics press release
