Neurosterix Announces Phase 1 Study of NTX-253 for Schizophrenia

A phase 1 study has commenced for NTX-253 for treatment of schizophrenia.¹ The positive allosteric modulator of muscarinic M4 receptor will be evaluated for safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy volunteers.

“The progression of NTX-253 into clinical studies represents an important milestone for both Neurosterix and Addex,” said Tim Dyer, chief executive officer of Addex Therapeutics. “Selective modulation of the M4 receptor through a PAM represents a novel therapeutic approach compared to traditional dopamine receptor antagonists and has the potential to provide patients suffering from schizophrenia with a differentiated efficacy and safety profile. We look forward to the progress of NTX-253 as it advances through clinical development.” Dyer’s comments and a focus on muscarinics in schizophrenia highlight the growing interest in nondopaminergic strategies to address the limitations of existing antipsychotic therapies.

Advancement of NTX-253 into phase 1 first-in-human clinical studies is supported by preclinical studies showing antipsychotic-like activity and a favorable safety profile. Studies for NTX-253 that have been completed will enable an Investigational New Drug Application with the US Food and Drug Administration.² A phase 1 trial is a critical early step in drug development, focusing on establishing the drug’s safety profile and behavior in humans generally; the study will use healthy volunteers in phase 1 before advancing into further phases with patient populations.

NTX-253 is an orally administered positive allosteric modulator selective of the M4 muscarinic receptor. With a muscarinic action, the drug has potential to reduce symptoms of psychosis while avoiding movement disorders and metabolic issues typically associated with traditional schizophrenia medications like dopamine antagonists. Neurosterix noted that preclinical studies of NTX-253 have shown robust antipsychotic-like activity in combination with a favorable safety profile. Previous research on this type of drug has shown that M4 positive allosteric modulators can indirectly affect dopamine levels, providing antipsychotic results without peripheral side effects commonly seen with direct agonists. Studies in rodent models have also shown M4 positive allosteric modulators to reverse in vivo effects of psychomotor stimulants that cause increases in extracellular dopamine.^3,4

If trials are successful, NTX-253 could join a new class of antipsychotic therapy and contribute to a broader shift in how schizophrenia is treated. Results from the phase 1 study will inform future clinical development and determine whether the drug advances into trials involving patients with schizophrenia.

References

1. Addex spin-out Neurosterix has started a phase 1 clinical study with M4 PAM - NTX-253 for schizophrenia. Press release. January 7, 2026. Accessed January 7, 2026. https://www.addextherapeutics.com/en/investors/press-releases/addex-spin-out-neurosterix-has-started-phase-1-clinical-study-m4-pam-ntx-253-schizophrenia/

2. Innovative treatments for central nervous system disorders. Addex Therapeutics. December 2025. Accessed January 7, 2026. https://www.addextherapeutics.com/files/2117/6484/9482/20251204_Addex_Corporate_Presentation_December_2025.pdf

3. Bubser M, Bridges TM, Dencker D, et al. Selective activation of M4 muscarinic acetylcholine receptors reverses MK-801-induced behavioral impairments and enhances associative learning in rodents. ACS Chem Neurosci. 2014;5(10):920-942.

4. Byun NE, Grannan M, Bubser M, et al. Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100. Neuropsychopharmacology. 2014;39(7):1578-1593.