Tazbentetol Demonstrates Early Symptom Improvement in Phase 2 Schizophrenia Trial
Key Clinical Summary
- Phase 2 interim data (n = 16) show greater Positive and Negative Syndrome Scale (PANSS) score reductions with tazbentetol vs placebo (−11.9 vs −5.6) after 6 weeks.
- Statistically significant improvement observed in positive symptoms (p = 0.01), with trends in negative symptoms.
- Favorable safety profile reported, with no severe adverse events and supportive EEG biomarker changes.
Interim results from a phase 2 randomized, double-blind, placebo-controlled trial of tazbentetol demonstrated early signals of efficacy across schizophrenia symptom domains. Manufacturer Spinogenix Inc presented the findings at the Schizophrenia International Research (SIRS) 2026 Annual Congress in Florence, Italy.
Study Findings
The ongoing phase 2 trial (NCT06442462) enrolled 32 adults with schizophrenia, though the interim analysis included 16 participants. Patients received either 300 mg oral tazbentetol or placebo daily for 6 weeks, with outcomes assessed through day 71.
Patients treated with tazbentetol showed greater improvement in overall symptom severity, with a mean reduction in Positive and Negative Syndrome Scale (PANSS) total score of −11.9 compared with −5.6 in the placebo group, a −6.3 point difference at day 71.
Positive symptoms improved significantly, with a −3.3 ± 0.88 (mean ± SEM) change in PANSS positive subscale versus −0.1 ± 0.66 in placebo (difference −3.2; p = 0.01). Negative symptoms also improved modestly, with a −1.8 ± 0.77 change compared with −1.0 ± 0.65 in placebo.
Electroencephalogram (EEG) biomarkers further supported the drug’s effect. Significant improvements were observed in gamma band power abnormalities in occipital (p = 0.011) and temporal regions (p = 0.008), as well as alpha band power in occipital regions (p = 0.002). Additional gamma improvements were noted in central regions under eyes-open conditions (p = 0.042).
No severe adverse events were reported, and the therapy was well tolerated.
Clinical Implications
Tazbentetol represents a novel synaptic regenerative approach aimed at restoring glutamatergic synapses, potentially targeting positive, negative, and cognitive symptoms simultaneously. The observed improvements in PANSS scores and normalization of EEG abnormalities suggest a biologically relevant mechanism of action. If confirmed in larger cohorts, this approach may shift treatment paradigms beyond symptomatic control.
However, given the small interim sample size, ongoing data from the full cohort and longer follow-up will be necessary to confirm efficacy, durability, and real-world applicability.
Expert Commentary
“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. He noted the findings provide “important preliminary clinical support for the role of synapse loss in the genesis of schizophrenia symptoms,” highlighting the potential to impact all symptom domains.
