EuMentis Therapeutics announced that the U.S. Food and Drug Administration has authorized its Investigational New Drug application to initiate a Phase 2 clinical trial of EM-221, an investigational phosphodiesterase 10A (PDE10A) inhibitor, in patients with schizophrenia. The company expects to begin dosing patients in the second half of 2025.
Novel Mechanism Targets Key Brain Pathways
EM-221 targets PDE10A, a key intracellular enzyme that regulates dopamine and glutamate signaling in brain regions implicated in schizophrenia. Unlike traditional antipsychotics that broadly block dopamine receptors and are associated with serious side effects such as weight gain, movement disorders, and sedation, PDE10A inhibition offers a more targeted mechanism that modulates these pathways without direct receptor antagonism.
"EM-221 is more than a single asset—it represents a pipeline in a product with potential applications across multiple neuropsychiatric and neurodevelopmental conditions," said Frank Stonebanks, Chief Executive Officer of EuMentis. "As we enter this next phase, we're excited by the opportunity to unlock significant therapeutic and commercial value in schizophrenia and beyond, supported by a world-class team and leading scientific collaborators."
Addressing Critical Treatment Gaps
The drug is designed as a next-generation, selective PDE10A inhibitor to maximize efficacy while minimizing off-target effects. Preclinical and phase 1 clinical studies suggest EM-221 may offer superior tolerability and a broader therapeutic window, positioning it as a potential best-in-class treatment for both the positive and negative symptoms of schizophrenia—a critical gap left unaddressed by current therapies.
"We are very excited to receive IND clearance from the FDA for schizophrenia, which is a serious, lifelong disorder affecting nearly 4 million adults and adolescents in the U.S. alone," said Dr. Randall Marshall, Chief Medical Officer of EuMentis. "There is a wealth of data suggesting that a PDE10A inhibitor can benefit individuals with schizophrenia as a more effective, safer, and better-tolerated therapy."
Expert Endorsement of Innovative Approach
Dr. John Krystal, Robert L. McNeil, Jr. Professor of Translational Research and Chair of Psychiatry at Yale School of Medicine, highlighted the significance of the PDE10A mechanism. "Despite decades of use, current dopamine receptor-blocking antipsychotic medications remain limited in their tolerability and effectiveness which make them unacceptable to many patients," he said. "The PDE10A mechanism represents an important and innovative approach to modulating dopaminergic and glutamatergic signaling in the brain. I'm encouraged by the potential of EM-221 to offer a new therapeutic option for patients who urgently need safer and more effective treatments."
Comprehensive Treatment Potential
EM-221 is uniquely concentrated in the brain's striatum, where it enhances cyclic nucleotide signaling and balances dopamine pathways. Unlike traditional antipsychotics, it offers the potential to address not only the positive symptoms like hallucinations but also the challenging negative symptoms—such as social withdrawal, blunted emotions and difficulty planning—that often persist untreated.
EuMentis describes EM-221 as building a "pipeline-in-a-product" approach, with potential applications across multiple neuropsychiatric and neurodevelopmental conditions beyond schizophrenia. The company is committed to leading innovation in the neuropsychiatric disease field by advancing programs that target selective CNS circuits in the brain with clinically validated mechanisms of action.
