EuMentis Therapeutics Receives U.S. FDA Clearance of IND Application for EM-221, a Novel PDE10A Inhibitor for Schizophrenia

-Company expects to initiate Phase 2 study in 2H 2025-

SAN DIEGO, July 30, 2025 /PRNewswire/ -- EuMentis Therapeutics, Inc., ("EuMentis"), a clinical-stage drug development company focused on advancing novel treatments for schizophrenia and other central nervous system (CNS) conditions, today announced that the U.S. Food and Drug Administration (FDA) has authorized 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 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.

"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.  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 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.

"Despite decades of use, current dopamine receptor-blocking antipsychotic medications remain limited in their tolerability and effectiveness which make 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 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." 

About EM-221

EuMentis is building a pipeline-in-a-product around EM-221. EM-221 is an innovative product that targets the phosphodiesterase 10A enzyme, uniquely concentrated in the brain's striatum, to enhance cyclic nucleotide signaling and balance 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.  EM-221 has been cleared by the U.S. FDA for Phase 2 evaluation, and the company expects to begin dosing in its first clinical trial in the second half of 2025.

About EuMentis Therapeutics

EuMentis is a clinical-stage drug development company focused on advancing novel treatments for schizophrenia and other central nervous system (CNS) conditions.  EuMentis 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. This approach will enable its therapies to achieve better efficacy and tolerability, with the goal to deliver improved outcomes for patients.  The Company's lead product, EM-221, is a potentially groundbreaking advancement in schizophrenia treatment, with a new, differentiated PDE10A inhibitor.  Developed through years of rigorous research, this breakthrough heralds a new era of hope, aiming to improve overall quality of life for those affected by schizophrenia with a novel mechanism that's both precise and promising. 

EuMentis is headquartered in San Diego, CA. For more information, please visit https://eumentistx.com and engage with us on LinkedIn.

Media Contact
Amy Conrad
Juniper Point
[email protected]
858-366-3243

Company Contact
Frank Stonebanks
CEO
[email protected]

SOURCE EuMentis Therapeutics, Inc.