EuMentis Therapeutics, Inc., a clinical-stage drug development company focused on advancing novel treatments for schizophrenia and other central nervous system (CNS) conditions, has announced that the US Food and Drug Administration (FDA) has authorised its Investigational New Drug (IND) application to initiate a Phase 2 clinical trial of EM–221, the company's investigational phosphodiesterase 10A (PDE10A) inhibitor, in patients with schizophrenia.

“This IND clearance represents a major milestone for EuMentis as we advance EM–221 through Phase 2 clinical development,” said Frank Stonebanks, Chief Executive Officer of EuMentis. “EM–221 is more than a single asset—it represents a pipeline in a product with potential applications across multiple neuropsychiatric and neurodevelopmental conditions. 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.”

EM-221 is targeting PDE10A, a key intracellular enzyme that regulates dopamine and glutamate signalling 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.

“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 US 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. We look forward to initiating our Phase 2 study of EM-221 later this year.”

EM–221 is a next-generation, selective PDE10A inhibitor designed to maximise efficacy while minimising 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.

“Despite decades of use, current dopamine receptor-blocking antipsychotic medications remain limited in their tolerability and effectiveness, which makes them unacceptable to many patients,” said Dr. John Krystal, Robert L. McNeil, Jr. Professor of Translational Research and Chair of Psychiatry at Yale School of Medicine. “The PDE10A mechanism represents an important and innovative approach to modulating dopaminergic and glutamatergic signalling in the brain.”