MILAN, Italy and MORRISTOWN, N.J., September 2, 2026

Newron Pharmaceuticals S.p.A. announced completion of screening for enrollment in its pivotal Phase III ENIGMA-TRS 1 study evaluating evenamide as an add-on therapy for patients with treatment-resistant schizophrenia (TRS). As of September 2, 996 patients had entered screening, 411 had been randomized, and 352 remained in the screening process. Based on the study’s stringent eligibility criteria and patients currently undergoing assessment, Newron expects to complete target enrollment of at least 600 randomized patients by mid-October 2026. Topline results from the initial 12-week treatment period are expected in Q1 2027, providing an important clinical development milestone for evenamide.

ENIGMA-TRS 1 Advances Toward Full Enrollment

ENIGMA-TRS 1 is an international, randomized, double-blind, placebo-controlled Phase III study designed to evaluate the efficacy, tolerability and safety of evenamide at 15 mg twice daily and 30 mg twice daily compared with placebo. The study is enrolling patients receiving second-generation antipsychotics, including clozapine, who meet the international Treatment Response and Resistance Psychosis (TRRIP) criteria for TRS. Before randomization, participants undergo a 42-day screening period during which their diagnosis, background antipsychotic plasma levels and protocol eligibility are assessed by an Independent Eligibility Assessment Committee comprising three international schizophrenia experts. The trial is being conducted across study centers in Europe, Asia, Latin America and Canada.

Primary Endpoint Set for Week 12

The primary efficacy assessment will occur 12 weeks after randomization, with the study’s primary endpoint defined as the change from baseline in Positive and Negative Syndrome Scale (PANSS) scores. Following the initial 12-week assessment, participants will remain in the double-blind, placebo-controlled study through 26 and 52 weeks, allowing Newron to evaluate longer-term efficacy and safety. The company said the rapid pace of enrollment reflects investigator interest in evenamide and its differentiated glutamatergic mechanism. Previous Phase 2 studies 014/015 and Phase 3 study 008A reported increasing efficacy when evenamide was used as an add-on therapy in patients with TRS and poorly responding schizophrenia, respectively, alongside a favorable safety and tolerability profile.

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Evenamide Targets Glutamatergic Dysfunction

Evenamide is an orally available investigational new chemical entity designed to provide a therapeutic approach distinct from currently marketed antipsychotics. The compound selectively blocks voltage-gated sodium channels (VGSCs) and is designed to normalize excessive glutamate release associated with aberrant sodium-channel activity without affecting basal glutamate levels. Newron believes this glutamatergic modulation could address biological mechanisms that are not directly targeted by conventional antipsychotics, which primarily act through dopamine pathways. With at least 600 patients expected to be randomized in ENIGMA-TRS 1 and the first 12-week results anticipated in Q1 2027, the study represents a key test of evenamide’s potential as an add-on treatment for patients whose symptoms remain inadequately controlled with existing antipsychotic therapy.

Source:Can-Fite BioPharma, press relese