MapLight Therapeutics (MPLT) Study result summary

Executive summary and unmet medical need

• Schizophrenia affects over 20 million globally, with more than 3 million in the U.S.; current treatments leave significant gaps, including high rates of inadequate response and discontinuation due to side effects.

• Cognitive impairment remains a major unmet need, affecting over 80% of patients and impacting long-term outcomes.

Study overview, design, and population

• Phase II ZEPHYR trial was a randomized, double-blind, placebo-controlled study at 25 U.S. sites, enrolling 307 adults with acute schizophrenia exacerbation, randomized to placebo, 210/3 mg BID, or 330/6 mg QD dosing arms.

• Participants had moderate to severe symptoms at baseline, with balanced demographics (mean age 40–42, majority male and Black or African American).

• Dosing involved a single-dose titration, with optional dose reduction for tolerability between weeks one and three; no fasting requirement and simple titration support real-world adherence.

• ML-007C-MA is an oral, extended-release, fixed-dose combination of an M1/M4 muscarinic agonist and a peripherally acting anticholinergic, designed to maximize central efficacy and minimize peripheral side effects.

Efficacy and cognitive outcomes

• The 210/3 mg BID dose met the primary endpoint, showing a statistically significant reduction in PANSS total score versus placebo (effect size 0.37, p=0.015); completer analysis showed a larger effect size of 0.5.

• Significant improvements were observed on secondary endpoints: CGI-S (effect size 0.48, p=0.002), PANSS positive subscale (effect size 0.39–0.56, p=0.012–0.0003), and cognitive composite score in the cognitively impaired subgroup (effect size 0.51, p=0.041), independent of psychotic symptom reduction.

• Participants on BID dosing were more likely to achieve a 30% PANSS response and readiness for discharge compared to placebo.

• The 330/6 mg QD dose showed numerical but not statistically significant improvement on the primary endpoint, though it separated from placebo on some secondary measures.