ML-007C-MA - (ZEPHYR)

July 27, 2026: MapLight Therapeutics, Inc. (NASDAQ: MPLT) reported positive topline Phase 2 ZEPHYR results for ML-007C-MA (oral M1/M4 muscarinic agonist betovumeline co-formulated with fesoterodine) in adults with acute exacerbation of schizophrenia. The trial (n=307; 25 U.S. sites) met its primary endpoint: the 210/3 mg twice-daily (BID) dose significantly improved PANSS total score vs placebo at Week 5 (LS mean difference -4.5; effect size 0.37; p=0.015). In a completer analysis, effect size was 0.50 (LS mean difference -6.0; p=0.002). Key secondary endpoints were significant for the BID arm, including CGI-S (ES 0.48; p=0.002) and PANSS positive Marder factor (ES 0.39; p=0.012). A prespecified cognitive endpoint in participants with baseline cognitive impairment improved vs placebo (Cogstate; ES 0.51; +0.44 points; p=0.041).

The 330/6 mg once-daily (QD) dose showed numerical improvement but missed the primary endpoint; some secondary endpoints were significant (e.g., CGI-S p=0.036). Safety was generally favorable with no serious or drug-related severe TEAEs reported in active arms; GI discontinuations were 2.0% at 210/3 mg BID.

Next steps: the company plans FDA End-of-Phase 2 meetings and a further registrational/confirmatory trial in schizophrenia. The ongoing Phase 2 VISTA trial in Alzheimer’s disease psychosis has topline results expected in 2H 2027. The company also noted prior Phase 2 IRIS results for ML-004 in ASD irritability (subgroup signal) and plans an FDA EOP2 meeting for that program.