MapLight Therapeutics’ stock crashed by more than 70% after the release of data from its Phase II schizophrenia trial, despite the study meeting its primary endpoint.
In the Phase II ZEPHYR trial (NCT07038876), ML-007C-MA, an oral M1/M4 muscarinic agonist (betovumeline) co-formulated with a peripherally acting anticholinergic (fesoterodine), demonstrated a statistically significant and clinically meaningful reduction in Positive and Negative Syndrome Scale (PANSS) total score compared to placebo after five weeks. The endpoint was met in the 210/3 mg twice-daily (BID) dose.
Discover B2B Marketing That Performs
Combine business intelligence and editorial excellence to reach engaged professionals across 36 leading media platforms.
In the modified intent-to-treat (mITT) population, the BID arm achieved an effect size of 0.37 (Cohen’s d), with patients experiencing a mean 4.5-point improvement in PANSS total score versus placebo.
In a prespecified analysis of patients who completed five weeks of treatment, the effect size was 0.50, with a least squares (LS) mean difference from placebo of six points.
ML-007C-MA also achieved significance on key secondary endpoints in the BID arm, including a 0.48 point difference in the Clinical Global Impression of Severity (CGI-S), and 0.39 points on PANSS positive Marder factor, as well as multiple other secondary and exploratory outcomes.
Dr Chris Kroeger, co-founder and CEO of MapLight: “We observed a robust signal on a pre-specified secondary cognition endpoint that appears independent of antipsychotic effect. Cognitive impairment affects the majority of people living with schizophrenia and remains an area where no therapy has yet been approved. We believe the combination of a significant effect on PANSS and other concordant endpoints, along with a meaningful effect on cognitive performance, represents a powerful, comprehensive overall efficacy profile in schizophrenia, and strengthens the rationale for our ongoing VISTA trial in Alzheimer’s disease psychosis and the broader indication expansion for ML-007C-MA.”
MapLight added that the 330/6 mg once-daily (QD) dose demonstrated numerical improvement over placebo in schizophrenia patients but did not achieve statistical significance on the primary endpoint. However, it did demonstrate significant separation on CGI-S, PANSS positive Marder factor, and Readiness for Discharge Questionnaire and numerical separation on several other endpoints.
At the 210/3 mg BID dose, treatment-emergent adverse events (TEAEs) were reported in 74.7% of patients compared with 48.1% receiving placebo, with most events mild in severity.
The Phase II data support progression to a registrational trial, with the company set to engage with the US Food and Drug Administration (FDA) at an end-of-Phase II meeting.
After announcing the mixed data, the company’s stock dropped significantly, by 71.9%, from a 23 July close of $35.23 to a 27 July close of $9.90. MapLight debuted on the Nasdaq in October 2025 with a $250m initial public offering (IPO) to raise funds for the ZEPHYR trial.
MapLight hopes for Cobenfy competitor
MapLight hopes to take on BMS’ Cobenfy (xanomeline and trospium chloride), which gained FDA approval for use in schizophrenia patients in September 2024. In 2025, Cobenfy brought in $155m for BMS. The approval marked the first new pharmaceutical option for schizophrenia patients in decades.
GlobalData expects Cobenfy to become the top-selling drug in the schizophrenia market with sales of $2.2bn across the seven major markets (7MM: US, France, Germany, Italy, Spain, the UK, and Japan) in 2031.
The schizophrenia market across the 7MM is poised to grow at a compound annual growth rate (CAGR) of 7.4% from $8.4bn in 2021 to $17bn in 2031, driven by the anticipated introduction of 11 late-stage pipeline products during the forecast period, according to GlobalData.
GlobalData’s latest report, “Schizophrenia: Seven-Market Drug Forecast and Market Analysis – Update”, reveals that the late-stage pipeline products are expected to capture a significant portion of the schizophrenia market, accounting for 33.4% of global sales in 2031, despite the atypical antipsychotics retaining the largest portion of patient shares.
GlobalData is the parent company of Clinical Trials Arena.
