Newron Pharmaceuticals has published peer-reviewed clinical data demonstrating that evenamide, a novel glutamate modulator, provides sustained and clinically meaningful benefits as an adjunctive therapy in patients with schizophrenia who show inadequate response to standard antipsychotics, including those with treatment-resistant schizophrenia (TRS).

The publication in Therapeutic Advances in Psychopharmacology, co-authored by Newron’s chief medical officer, Ravi Anand, MD, highlights analyses from multiple randomised clinical studies and provides a mechanistic rationale for targeting glutamatergic dysfunction in the hippocampus, a region implicated in schizophrenia pathophysiology. The data indicate that evenamide may improve not only positive and negative symptoms but also social functioning and life engagement, domains often poorly addressed by existing therapies.

Anand said: “This publication captures more than a decade of scientific and clinical work addressing one of psychiatry’s most difficult challenges. The analyses highlight not only symptom improvement but also real-world functional gains that matter to people living with schizophrenia, particularly those who have exhausted available options.”

Evenamide’s mechanism of action differs from current antipsychotics, which primarily block dopamine receptors in the basal ganglia. By selectively reducing excessive glutamate activity in the hippocampus, evenamide indirectly modulates dopamine signalling while preserving normal neuronal function. According to the company, this hippocampal site of action may explain the improvements observed in symptoms, social engagement, and functional outcomes.

Across reported clinical studies, evenamide has shown a favourable safety and tolerability profile, with low rates of treatment discontinuation and no consistent serious safety concerns.

The publication includes data from two key programmes. In a one-year study of patients with TRS, over half improved sufficiently to no longer meet TRS severity criteria, while approximately one-quarter achieved remission under stringent criteria. In a separate randomised, double-blind, placebo-controlled trial, evenamide showed statistically significant benefits over standard of care, regardless of prior treatment failures.

Anand added: “Evenamide represents a fundamentally different treatment approach. By targeting the hippocampus – the source of the deficit rather than its downstream effects – we believe evenamide has the potential to shift the treatment paradigm, particularly for patients with TRS who urgently need new options.”

Newron is progressing evenamide through its ENIGMA-TRS Phase 3 programme, comprising ENIGMA-TRS 1 and ENIGMA-TRS 2, to evaluate efficacy, safety, and tolerability in patients with documented TRS. Successful trials could support the use of evenamide as a first-in-class adjunctive therapy for patients with limited response to currently available antipsychotics.