Newron Begins Enrollment in Pivotal Phase III ENIGMA-TRS Program With Evenamide as Add-on Therapy in Patients With Treatment-Resistant Schizophrenia (TRS)

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ENIGMA-TRS 1 is an international, one-year, double-blind, placebo-controlled Phase III study in at least 600 patients; 12-week study results expected in Q4 2026

Evenamide, a first-in-class glutamate modulator, has the potential to be the first add-on therapy for TRS patients and for poorly responding patients with schizophrenia

Unique glutamatergic modulation mechanism of action offers new therapeutic option for this patient population

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Thanks for the information ! From what I understand, NMDA hypofunction could cause a surge of glutamate, resulting in excitotoxicity. Evenamide is supposed to calm this excitotoxicity with voltage-gated sodium channels.

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SPG302, in phase 2 , on the other hand, is supposed to regenerate glutamatergic synapses, which are lost in schizophrenia.

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Glutame as a neurotransmitter is not a glutamatergic synapse. So these molecules are not antagonistic.

And mGluR2/3 agonists have been in clinical trials for schizophrenia based on the NMDA hypofunction hypothesis but they have unfortunately failed. I hope this new mechanism of action will succeed. The results of their phase 2 studies are promising !

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https://www.businesswire.com/news/home/20250811493586/en/Newron-Notes-the-Publication-of-New-Preclinical-Research-Suggesting-Evenamide-Ameliorates-Schizophrenia-Related-Dysfunction "

New findings published in Neuropsychopharmacology are the first to demonstrate that evenamide targets the key site of schizophrenia pathology in the hippocampus, and so could be an ideal therapeutic agent for treatment of the disorder

Systemic, acute administration of evenamide in the neurodevelopment MAM model of schizophrenia improved positive, negative and cognitive symptoms of schizophrenia"

This is very good news

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