MapLight Stock Plunges After Schizophrenia Trial Splits on Dosage

MapLight Therapeutics lost more than 60% of its value within hours on Monday after a 307-patient schizophrenia trial split down the middle: one dose beat placebo, the other didn’t. Shares fell from Friday’s close of $36.56 to $13.76 by 10:30 a.m. Eastern, and kept sliding afterward, changing hands near $9.90 in the days since, nearly 73% below where they started.

The Nasdaq-listed neuroscience biotech built its entire public story around beating Bristol Myers Squibb’s Cobenfy, the first new schizophrenia drug approved in decades. Monday’s data did not kill that story. It complicated it, and quietly opened a second, bigger one about Alzheimer’s disease.

Two Doses, One Winner

The Phase 2 ZEPHYR trial enrolled adults experiencing an acute exacerbation of schizophrenia and tested two regimens of ML-007C-MA, an oral M1/M4 muscarinic agonist known generically as betovumeline and co-formulated with the anticholinergic fesoterodine to blunt gut and bladder side effects. MapLight had designed the 307-patient study to test a twice-daily and a once-daily version against placebo over five weeks.

Only one worked on paper.

The twice-daily arm posted an effect size, measured as Cohen’s d, of 0.37, and it also won on secondary measures including the Clinical Global Impression of Severity scale. Safety looked clean at both doses. MapLight reported one severe adverse event, a case of pneumonia, and called it unrelated to the drug.

Chris Kroeger, M.D., MapLight’s co-founder and chief executive, framed the split as a net positive. “We are very encouraged by these results, which show that ML-007C-MA delivered clinically meaningful antipsychotic efficacy alongside a favorable tolerability profile designed to translate into real-world use,” he said in the release announcing the data.

Three Analysts Land in Three Different Places

Investors did not share the enthusiasm. The stock’s slide past $13.76 and down toward $9.90 has left it well under even the most bearish new price targets, and Wall Street itself can’t agree on what the miss actually costs the company.

• Wolfe Research cut its target to $30 from $60 while keeping an Outperform rating, arguing the data support a real drug but show no clear edge over Cobenfy.
• Raymond James cut its target to $35 from $46, yet raised its odds of eventual approval in schizophrenia to 70% from 60%, even as it trimmed its peak sales estimate to roughly $1.1 billion from about $1.6 billion.
• BMO Capital analysts held that opportunity remains, pointing to a 6-point PANSS gap among patients who completed all five weeks of treatment, wider than the 4.5-point gap in the full study population.

Needham had lifted its target to $45 from $42 earlier in July, before the ZEPHYR data landed, and has not yet updated its call. Even after the cuts, analyst targets still range from $25 to $60, and the average rating on the stock remains some form of buy.

“But we contest that opportunity remains in schizophrenia,” the BMO Capital analysts wrote in a note to clients Monday, comparing ML-007C-MA’s numbers directly against Cobenfy’s own trial results, which posted a larger PANSS reduction.

The Cognition Signal Kroeger Keeps Repeating

Buried in the twice-daily arm’s data is the detail Kroeger returned to more than once: a win on cognitive impairment that showed up independent of how much a patient’s psychosis improved.

Cognitive impairment affects the majority of people living with schizophrenia and remains an area where no therapy has yet been approved.

Kroeger said that finding, paired with the drug’s tolerability, should also bode well for MapLight’s separate Alzheimer’s program. BMO’s analysts read the same result the same way. “Improvements in cognition were not associated with PANSS changes, suggesting ML-007C-MA’s M1 muscarinic targeting mechanism could provide improvements on cognition independent of improvements in schizophrenia symptoms,” they wrote.

Cognition problems in schizophrenia are common and stubborn; Karuna Therapeutics ran its own post-hoc look at cognitive impairment in a Phase 2 KarXT study before Cobenfy ever reached the market, and never turned it into an approved claim. If MapLight’s signal holds up, it would address a symptom cluster that current antipsychotics, including Cobenfy, still don’t touch.

Why Alzheimer’s Psychosis Could Be the Bigger Opportunity

Alzheimer’s disease psychosis has no approved drug, hits a large share of dementia patients, and is exactly where BMO’s analysts said they see the most upside for ML-007C-MA, mainly because it produced fewer side effects like constipation that matter disproportionately for elderly patients.

MapLight is already running a 300-patient Phase 2 trial called VISTA, testing the same 210/3 mg twice-daily dose that just hit its mark in schizophrenia, this time against hallucinations and delusions tied to Alzheimer’s disease. The FDA granted the program Fast Track designation in January 2026. Psychotic symptoms tied to hallucinations and delusions in roughly 40% of Alzheimer’s patients at some point in their illness, and the condition is linked to faster cognitive decline, higher rates of institutionalization and higher mortality.

A drug that eases those symptoms with a cleaner side effect profile than existing options would fill a gap nothing on the market currently covers. That is the bet BMO is making out loud while the stock chart says otherwise.

Cobenfy Already Learned This Lesson

The market MapLight is now leaning toward has already tested one muscarinic drug’s limits. Cobenfy, built on Karuna’s xanomeline-trospium combination, won approval in September 2024 as the first new schizophrenia drug in decades, and Cantor Fitzgerald analysts once projected it could reach $1 billion in annual sales by 2026.

The real number came in lower. Cobenfy generated $155 million in sales in 2025, and Bristol Myers has had to battle deeply ingrained prescribing habits among psychiatrists used to older antipsychotics, according to a BioSpace report on the launch. Its list price runs about $1,850 a month, or roughly $22,500 a year.

Cobenfy’s own push into Alzheimer’s-related psychosis stumbled in a clinical setback last year, according to PharmaVoice, and Leerink Partners subsequently cut its long-term sales forecast for the drug to $2.6 billion by 2030 from an earlier $5.8 billion. That failure is precisely why BMO and MapLight see the Alzheimer’s psychosis field as still open. Bristol Myers tried and did not close it out.

MapLight raised $250 million in an October 2024 initial public offering built specifically to fund the ZEPHYR trial and chase Cobenfy’s territory. Monday’s split result means that original bet only half paid off, even as it hands the company a second, less crowded market to chase instead.

The FDA Meeting That Decides Phase 3

MapLight said it plans an End-of-Phase 2 meeting with the FDA to map out a Phase 3 program for the twice-daily dose in schizophrenia, using ZEPHYR data as the foundation for an eventual new drug application. The company is also running further analyses on the once-daily dose before deciding whether to carry it forward at all.

Schizophrenia and Alzheimer’s are not the only bets on the table.

• Autism spectrum disorder – a Phase 2 candidate already in testing.
• Three preclinical programs – earlier-stage central nervous system projects still years from human trials.
• The SandboxAQ collaboration – a deal with Alphabet’s AI spinout, worth up to $200 million in upfront and milestone payments, aimed at using SandboxAQ’s AQBioSim platform to find new CNS drug targets built around a novel G protein-coupled receptor.

MapLight expects topline data from the Alzheimer’s disease psychosis trial in the second half of 2027, the same broad window in which a schizophrenia Phase 3 program would need its own results.

Disclaimer: This article covers clinical trial results and stock movements for informational purposes only and is not investment or medical advice; biotech share prices and drug development outcomes are highly uncertain, and readers should consult a licensed financial or medical professional before acting on this information. Figures are accurate as of publication.