MapLight's ML-007C-MA hits primary endpoint, company plans confirmatory pivotal trial

MapLight Therapeutics announced on July 27, 2026, topline results from its Phase 2 "ZEPHYR" trial evaluating ML-007C-MA in inpatient adult participants with schizophrenia experiencing an acute exacerbation of psychosis.¹

The study was designed with N=307, randomized 1:1:1 across placebo (N=104), ML-007C-MA 210/3 mg BID (N=101), and ML-007C-MA 330/6 mg QD (N=102), at 25 U.S. sites, with the primary endpoint of change from baseline PANSS Total Score at Week 5.¹

For the 210/3 mg BID arm, the LS mean change from baseline was -11.7 versus -7.2 for placebo, a difference of -4.5 points versus placebo, with p=0.015 and an effect size of 0.37, based on the mITT population.¹ In a prespecified completer analysis, the LS mean difference versus placebo was -6.0 points, with p=0.002 and an effect size of 0.50.¹ The 330/6 mg QD arm showed a difference of -2.8 versus placebo with p=0.110, not reaching statistical significance.¹

On the prespecified cognitive endpoint using the Cogstate battery, the 210/3 mg BID arm showed an LS mean difference of 0.44 versus placebo, with p=0.041 and an effect size of 0.51, among participants with baseline cognitive impairment.¹ The company reported no observed significant relationship between cognitive improvement and PANSS change, with r=-0.187, p=0.314 for the BID arm.¹

On safety, no serious or drug-related severe TEAEs occurred with either dose, and the only severe TEAE, pneumonia, was assessed as unrelated to study drug.¹ All-cause discontinuation was 19.9% across active treatment arms, with discontinuation due to TEAE at 7.1% and due to GI TEAE at 2.0% in the 210/3 mg BID arm.¹

MapLight said ZEPHYR-2 (Study 311) is planned as an additional pivotal trial evaluating 210/3 mg BID versus placebo, intended together with completed Study 211 to support initial NDA submission, with FDA engagement planned at an end-of-Phase 2 meeting.¹ Separately, the ongoing VISTA trial (Study 221) evaluating ML-007C-MA in Alzheimer's disease psychosis patients is expected to report topline results in the second half of 2027.¹