MILAN, Italy and MORRISTOWN, N.J.

September 25, 2026 — Newron Pharmaceuticals announced that the U.S. clinical hold on enrollment in its Phase 3 ENIGMA-TRS 2 study of evenamide remains in place, while the trial continues at sites outside the United States. The company is initiating an expansion of clinical sites and enrollment across Europe, Asia and Latin America to support continued development of evenamide for treatment-resistant schizophrenia (TRS). Approximately 80 patients have entered screening to date, and the study is expected to enroll at least 400 patients following completion of the 42-day screening period. Newron said it expects additional written communication from the U.S. Food and Drug Administration (FDA) regarding the hold and any potential protocol changes required before it can be lifted.

ENIGMA-TRS 2 Continues International Enrollment

ENIGMA-TRS 2 is a randomized, double-blind, placebo-controlled Phase 3 study evaluating 15 mg twice-daily evenamide in patients with treatment-resistant schizophrenia. The trial is designed to enroll at least 400 patients and assess efficacy, tolerability and safety over 12 weeks, with the primary efficacy and safety analysis conducted at the end of the treatment period. Newron initiated ENIGMA-TRS 2 in the United States in December 2025 following FDA and institutional review board approvals. The FDA placed enrollment of new U.S. patients on hold in April 2026 after Newron reported the sudden unexpected death of a study participant at a clinical site outside the United States. According to Newron, the investigator assessed the event as unrelated to study treatment, and the independent international safety monitoring board reviewed the event and recommended continuation of the ENIGMA-TRS program. No U.S. patients had been dosed with evenamide in ENIGMA-TRS 2 at the time of the announcement.

Evenamide Targets Glutamate Modulation in TRS

Evenamide is an investigational glutamate modulator designed to address excessive glutamate release associated with treatment-resistant schizophrenia. The ENIGMA-TRS development program is evaluating whether adding evenamide to existing antipsychotic treatment can improve symptoms in patients who have responded inadequately to available therapies. ENIGMA-TRS 1 is a separate international 52-week, randomized, double-blind, placebo-controlled Phase 3 study evaluating 15 mg twice daily and 30 mg twice daily evenamide versus placebo. The study includes patients receiving second-generation antipsychotics, including clozapine, who meet international consensus criteria for treatment-resistant schizophrenia. Its primary efficacy endpoint is the change from baseline in Positive and Negative Syndrome Scale (PANSS) score at Week 12.

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ENIGMA-TRS 1 Data Expected in Q1 2027

Newron expects to report the 12-week primary endpoint results from ENIGMA-TRS 1 in the first quarter of 2027. The study is being conducted across approximately 20 countries in Europe, Asia, Latin America and Canada, with the company expecting at least 600 patients to have been enrolled by mid-October 2026. After the initial 12-week assessment, ENIGMA-TRS 1 will continue under double-blind, placebo-controlled conditions through the 26- and 52-week time points. Meanwhile, ENIGMA-TRS 2 will continue expanding outside the United States while the FDA hold remains under review. The two Phase 3 studies are intended to provide the clinical evidence needed to evaluate the efficacy and safety of evenamide in treatment-resistant schizophrenia, with the ENIGMA-TRS 1 readout representing the next major planned clinical data milestone.

Source :Newron Pharmaceuticals press release