Tazbentetol for Schizophrenia Shows Symptom Improvement in Phase 2 Trial

Interim results from a phase 2 trial of tazbentetol for treatment of schizophrenia showed trends of improving positive and negative symptoms in patients via synaptic regeneration.¹ The safety profile was overall favorable, and biomarker signals indicated improvements in cortical abnormalities associated with schizophrenia, according to interim analysis presented at the Schizophrenia International Research Society 2026 Annual Congress.

"These results showcase the possibility for synaptic regeneration to shift our treatment approach in schizophrenia," said David Walling, PhD, chief clinical officer at CenExel and principal investigator of the trial, in a press release. "This study provides important preliminary clinical support for the role of synapse loss in the genesis of schizophrenia symptoms, with regeneration offering an intervention potentially impacting all symptom domains. I am eager to see continued promising data, including EEG analysis, as the trial progresses," he added.

The randomized, double-blind, placebo-controlled phase 2 trial enrolled 32 adults aged 18 to 65 with a diagnosis of schizophrenia.² Patients received a once-daily oral administration of 300 mg tazbentetol for 6 weeks, to evaluate the safety, efficacy, tolerability, and pharmacodynamics of the medication. Individuals included in the study were actively prescribed only 1 antipsychotic medication and were on a stable dose for at least 4 weeks. History of cardiac disease, malignancy, notable central nervous system event or diagnosis in the last 5 years, or use of other investigational products were key participant exclusion criteria.

At 6 weeks, primary outcomes were measured by Positive and Negative Symptom Scale (PANSS) scores, electroencephalogram (EEG) to assess brain activity, and change in smooth pursuit eye tracking.² Secondary outcomes included safety and tolerability measured by adverse events, change in Clinical Global Impression of Improvement score, change in MATRICS Consensus Cognitive Battery, World Health Organization Quality of Life questionnaire, and change in Personal and Social Performance score.

Interim assessment of a prespecified group of 16 patients (8 treatment and 8 placebo) from the phase 2 trial indicated improvement in both positive and negative symptoms, as well as normalization of schizophrenia-related abnormalities in brain activity. The safety profile was favorable and the medication was well-tolerated, with no severe adverse events. Participants receiving tazbentetol showed greater reductions in PANSS scores compared with placebo (mean change of -11.1 for treatment vs -5.5 for placebo). Tazbentetol was associated with significant improvements in EEG abnormalities related to schizophrenia: gamma band power abnormalities in the occipital and temporal regions were significantly improved (P = 0.011 and P = 0.008, respectively). Alpha band power abnormalities showed improvement in occipital regions in an eyes closed condition (P = 0.002), and gamma power also improved in central regions in an eyes open condition (P = 0.042).

Tazbentetol is a first-in-class investigational synaptic regenerative therapy. The drug is designed to trigger neurons to produce new synapses, restoring cognitive, motor, and other functions. This medication promotes formation of dendritic spines which have glutamatergic synapses, intending to reduce symptoms of schizophrenia.³ Other studies are also testing the use of tazbentetol for Alzheimer disease and amyotrophic lateral sclerosis.

References

1. Spinogenix reports early improvements in phase 2 trial of tazbentetol in patients with schizophrenia at the Schizophrenia International Research Society (SIRS) 2026 Annual Congress. Press release. March 26, 2026. Accessed March 26, 2026. https://www.prnewswire.com/news-releases/spinogenix-reports-early-improvements-in-phase-2-trial-of-tazbentetol-in-patients-with-schizophrenia-at-the-schizophrenia-international-research-society-sirs-2026-annual-congress-302725950.html?tc=eml_cleartime

2. Study of SPG302 in adults with schizophrenia. ClinicalTrials.gov. February 6, 2026. Accessed March 26, 2026. https://clinicaltrials.gov/study/NCT06442462?term=spinogenix&rank=2

3. Tazbentetol. AlzForum. Accessed March 26, 2026. https://www.alzforum.org/therapeutics/tazbentetol